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Ronald Marks
Emeritus Professor of Dermatology and
Former Head of Department of Dermatology
University of Wales College of Medicine
Cardiff, UK
Clinical Professor
Department of Dermatology and Skin Surgery
University of Miami School of Medicine
Miami, USA
Hodder Arnold
What do you think about this book? Or any other Arnold title?
Please send your comments to feedback.arnold@hodder.co.uk
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Contents
Preface
viii
1
1
2
11
12
12
14
15
17
19
20
23
25
26
27
29
35
4 Skin infections
Fungal disease of the skin/the supercial mycoses/infections
with ringworm fungi (dermatophyte infections)
Bacterial infection of the skin
Viral infection of the skin
Summary
37
58
58
63
65
69
70
37
44
50
56
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Contents
71
71
75
77
77
77
80
82
83
84
87
89
90
91
92
95
97
98
99
99
100
100
100
101
101
102
104
8 Eczema (dermatitis)
Atopic dermatitis
Seborrhoeic dermatitis
Discoid eczema (nummular eczema)
Eczema craquele (asteatotic eczema)
Lichen simplex chronicus (circumscribed neurodermatitis)
Contact dermatitis
Venous eczema (gravitational eczema; stasis dermatitis)
Summary
105
105
114
117
118
119
121
125
126
128
128
142
144
147
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Contents
149
149
162
168
169
171
171
173
177
178
179
180
182
182
183
183
184
186
188
188
192
194
197
198
199
200
200
201
202
204
205
207
207
207
219
224
226
227
227
233
237
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Contents
238
238
240
240
241
242
243
243
245
246
247
249
251
252
252
254
256
257
259
259
265
266
267
268
268
276
279
281
281
285
288
289
291
292
292
293
293
20 Disorders of pigmentation
Generalized hypopigmentation
Localized hypopigmentation
295
296
297
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Contents
Hyperpigmentation
Summary
299
302
303
303
305
305
309
311
314
316
Bibliography
317
Index
319
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Preface
Recognition and treatment of skin disease is an important part of the practice of
medicine. These skills should form an essential part of the undergraduate curriculum because skin disorders are common and often extremely disabling in one
way or another. Apart from the fact that all physicians will inevitably have to cope
with patients with rashes, itches, skin ulcerations, inamed papules, nodules and
tumours at some point in their careers, skin disorders themselves are intrinsically
fascinating. The fact that their progress both in development and in relapse can be
closely observed, and their clinical appearance easily correlated with their pathology, should enable the student or young physician to obtain a better overall view
of the way disease processes affect tissues.
The division of the material in this book into chapters has been pragmatic,
combining both traditional clinical and disease process categorization, and after
much thought it seems to the author that no one classication is either universally
applicable or completely acceptable.
It is important that malfunction is seen as an extension of normal function
rather than as an isolated and rather mysterious event. For this reason, basic structure and function of the skin have been included, both in a separate chapter and
where necessary in the descriptions of the various disorders.
It is intended that the book full both the educational needs of medical students and young doctors as well as being of assistance to general practitioners in
their everyday professional lives. Hopefully it will also excite some who read it sufciently to want to know more, so that they consult the appropriate monographs
and larger, more specialized works.
In this new edition of Roxburghs Common Skin Diseases account has been taken
of recent advances both in the understanding of the pathogenesis of skin disease
and in treatments for it. Please forgive any omissions as events move so fast it is
really hard to catch up!
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C H A P T E R
An introduction to skin
and skin disease
An overview
Summary
11
An overview
Skin is an extraordinary structure. We are absolutely dependent on this 1.7 m2 of
barrier separating the potentially harmful environment from the bodys vulnerable
interior. It is a composite of several types of tissue that have evolved to work in
harmony one with the other, each of which is modied regionally to serve a different function (Fig. 1.1). The large number of cell types (Fig. 1.2) and functions of
the skin and its proximity to the numerous potentially damaging stimuli in the
environment result in two important considerations. The rst is that the skin is
frequently damaged because it is right in the ring line and the second is that
Stratum corneum
SC (15 m)
E (3550 m)
Granular cell layer
HF
D (12 mm)
ESG
SFL
Malpighian layer
Basal layer
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each of the various cell types that it contains can go wrong and develop its own
degenerative and neoplastic disorders. This last point is compounded by the ready
visibility of skin, so that minor deviations from normal give rise to a particular set
of signs. The net effect is that there seems to be a large number of skin diseases.
Skin disease is very common. However healthy we think our skin is, it is likely
that we will have suffered from some degree of acne and maybe one or other of
the many common skin disorders. Atopic eczema and the other forms of eczema
affect some 15 per cent of the population under the age of 12, psoriasis affects 12
per cent, and viral warts, seborrhoeic warts and solar keratoses affect large segments of the population. It should be noted that 1015 per cent of the general
practitioners work is with skin disorders, and that skin disease is the second commonest cause of loss of work. Although skin disease is not uncommon at any age,
it is particularly frequent in the elderly.
Skin disorders are not often dramatic, but cause considerable discomfort and
much disability. The disability caused is physical, emotional and socioeconomic,
and patients are much helped by an appreciation of this and attempts by their
physician to relieve the various problems that arise.
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THE EPIDERMIS
The epidermis contains keratinocytes mainly, but also non-keratinocytes
melanocytes and Langerhans cells. This cellular structure is some three to ve
cell layers thick on average, 3550 m thick in absolute terms (Fig. 1.7a). Not
unexpectedly, the epidermis is about two to three times thicker on the hands and
feet particularly the palms and soles. The epidermis is indented by nger-like
projections from the dermis known as the dermal papillae (Fig. 1.7b) and rests on
a complex junctional zone which consists of a basal lamina and a condensation of
dermal connective tissue (Fig. 1.8).
The cells of the epidermis are mainly keratinocytes containing keratin tonolaments, which are born in the basal generative compartment and ascend through
the Malpighian layer to the granular cell layer. They are joined to neighbouring
keratinocytes by specialized junctions known as desmosomes. These are visible as
prickles in formalin-xed sections but as alternating light and dark bands on
electron microscopy. In the granular layer, they transform from a plump oval or
rectangular shape to a more attened prole and lose their nucleus and cytoplasmic
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(a)
(b)
Figure 1.7 (a) Photomicrograph of normal epidermis (H & E, 90). (b) Photomicrograph of the underside of a sheet
of epidermis after removal from dermis showing the indentations made by the nger-like dermal papillae.
Collagen fibre
Tonofilaments
Attachment plaque
Plasma membrane
Lamina lucida
Basal lamina
Dermal microfibril
bundle
organelles. In addition, they develop basophilic granules containing a histidinerich protein known as laggrin and minute lipid-containing, membrane-bound
structures known as membrane-coating granules or lamellar bodies.
These alterations are part of the process of keratinization during which the
keratinocytes differentiate into tough, disc-shaped corneocytes. Other changes
include reduction in water content from 70 per cent in the keratinocytes to the
stratum corneums 30 per cent, and the laying down of a chemically resistant,
cross-linked protein band at the periphery of the corneocyte.
Of major importance to the barrier function of the stratum corneum is the intercellular lipid which, unlike the phospholipid of the epidermis below, is mainly polar
ceramide and derives from the minute lamellar bodies of the granular cell layer.
It takes about 28 days for a new keratinocyte to ascend through the epidermis
and stratum corneum and desquamate off at the skin surface. This process is
greatly accelerated in some inammatory skin disorders notably psoriasis.
Pigment-producing cells
Black pigment (melanin) synthesized by melanocytes protects against solar ultraviolet radiation (UVR). Melanocytes, unlike keratinocytes, do not have desmosomes,
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Dendrites
Nucleus
Nucleolus
Developing melanosomes
stages IIV
but have long, branching dendritic projections that transport the melanin they
synthesize to the surrounding cells (Fig. 1.9). They originate from the embryonic
neural crest. Melanocytes account for 510 per cent of cells in the basal layer of the
epidermis. Melanin is a polymer, synthesized from the amino acid tyrosine with
the help of a copper-containing enzyme, tyrosinase. Exposure to the sun accelerates
melanin synthesis, which explains suntanning.
Skin colour is mainly due to melanin and blood. Interestingly, the number of
melanocytes in skin is the same regardless of the degree of racial pigmentation
it is the rate of pigmentation that differs.
Langerhans cells
Langerhans cells are also dendritic cells, but are found within the body of the epidermis in the Malpighian layer rather than in the basal layer. They derive from the
reticuloendothelial system and have the function of picking up foreign material
and presenting it to lymphocytes in the early stages of a delayed hypersensitivity
reaction. They are reduced in number after exposure to solar UVR, accounting for
the depressed delayed hypersensitivity reaction in chronically sun-exposed skin.
THE DERMIS
The tissues of the dermis beneath the epidermis are important in giving mechanical
protection to the underlying body parts and in binding together all the supercial
structures. It is composed primarily of tough, brous collagen and a network of
bres of elastic tissue, as well as containing the vascular channels and nerve bres
of skin (Fig. 1.10). There are about 20 different types of collagen, but the adult
dermis is made mainly of types I and III, whereas type IV is a major constituent
of the basal lamina of the dermo-epidermal junction. Between the bres of collagen
is a matrix composed mainly of proteoglycan in which are scattered the broblasts that synthesize all the dermal components. Collagen bundles are composed of
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Collagen fibres
Tropocollagen ~240 nm
Collagen fibre or fibril
Fibroblast
Bundle of collagen
fibres in cross section
Diameter of individual
fibres varies from
20 to 120 nm.
64 nm Periodicity in
long section of fibre
Elastic tissue has two
components:
Microfibrils
Amorphous substance
Elastic fibres
The ratio of
fibrils to
amorphous
substance
varies. High
in papillary
and low in
reticular dermis.
(b)
(a)
Figure 1.10 (a) Diagram to show components of the dermis. (b) Photomicrograph to show dermal structure.
Stratum
corneum
Epidermis
Papillary capillary
Dermis
Subcutaneous
fat
There are no blood vessels in the epidermis and the necessary oxygen and nutrients
diffuse from the capillaries in the dermal papillae. These capillaries arise from horizontally arranged plexuses in the dermis (Fig. 1.11).
Nerve structures
Recently, very ne nerve bres have been identied in the epidermis, but most of
the bres run alongside the blood vessels in the dermal papillae and deeper in the
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Figure 1.12
Photomicrographs to
show (a) Paccinian
corpuscle and
(b) Meissner corpuscle
specialized neural
receptors (H & E, 150).
(a)
(b)
dermis. There are several types of specialized sensory receptor in the upper dermis
that detect particular sensations (Fig. 1.12).
Hair follicles are arranged all over the skin surface apart from the palms and soles,
the genital mucosa and the vermilion of the lips. Hair growth is asynchronous in
humans but synchronous in many lower mammals. The different phases of our
asynchronous hair growth occur independently in individual follicles but are
timed to occur together in synchronous hair growth, accounting for the phenomenon of moulting in small, furry mammals. The phase of the hair growth is
known as anagen and is the longest phase of the hair cycle. Following anagen, a
short stage of defervescence is reached known as catagen. This is followed by a
resting phase known as telogen, which is again followed by anagen somewhat later
(Fig. 1.13).
The hair shaft grows from highly active, modied epidermal tissue known as
the hair matrix. The shaft traverses the hair follicle canal, which is made up of a
series of investing epidermal sheaths, the most prominent of which is the external
root sheath (Fig. 1.14). The whole follicular structure is nourished by a small
indenting cellular and vascular connective tissue papilla, which pokes into the
base of the matrix. The sebaceous gland secretes into the hair canal a lipid-rich
substance known as sebum, whose function is to lubricate the hair (Fig. 1.15).
Sebum contains triglycerides, cholesterol esters, wax esters and squalene. Hair
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Anagen
Catagen
Telogen
Remnant of i
root sheath
Inner root
sheath
Sebaceo
duct
Outer root
sheath
Outer root
sheath
ub
Inner root
sheath
Early anagen
Club
Sebaceous
gland
Telogen
lub hair
b
agen hair
Dermal papilla
Basal lamina
Dermal papilla
Dermal papilla
Dermal papilla
Epidermis
Sebaceous gland
Hair matrix
(a)
Hair papilla
(b)
growth and sebum secretion are mainly under the control of androgens, although
other physiological variables may also inuence these functions.
The eccrine sweat glands are an extremely important part of the bodys
homeothermic mechanism in that the sweat secretion evaporates from the skin
surface to produce a cooling effect. Apart from heat, eccrine sweat secretion may
also be stimulated by emotional factors and by fear and anxiety. Certain body
sites, such as the palms, soles, forehead, axillae and inguinal regions, secrete sweat
selectively during emotional stimulation.
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(a)
(b)
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Summary
The eccrine sweat glands consist of a coiled secretory portion deep in the dermis
next to the subcutaneous fat and a long, straight, tubular duct whose nal portion is coiled and penetrates the epidermis to drain at the sweat pore on the surface (Fig. 1.16). The gland and its duct are lined by a single layer of secretory cells
and surrounded by myoepithelial cells.
The apocrine sweat glands drain directly into hair follicles in the axillae and
groins. They are larger than eccrine sweat glands and the secretum is completely
different, being semi-solid and containing odiferous materials that are thought to
have the function of sexual attraction.
Summary
Skin diseases account for about 15 per cent of a
general practitioners workload.
Acne, eczema, psoriasis, warts and skin tumours
are amongst the commonest of all human
disorders.
Skin is the protective interface between the
potentially injurious external environment and the
vulnerable organs and tissues of the body.
The keratinocytes in the epidermis mature into the
attened corneocytes of the stratum corneum. The
stratum corneum prevents water loss, penetration
by substances in contact with the skin and invasion
by micro-organisms.
Keratinocytes are constantly dividing in the basal
layer of the epidermis and corneocytes are shed at
the surface.
Melanocytes are dendritic, pigment-producing cells
in the basal layer of the epidermis.
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C H A P T E R
12
14
15
17
Secondary changes
19
20
Summary
23
ERYTHEMA
The degree of erythema depends on the degree of oxygenation of the blood, its rate
of flow and the site, number and size of the skins blood vessels. Different disorders
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tend to be associated with particular shades of red. Psoriatic plaques, for example,
tend to be dark red in colour rather than pink, bright red or bluish red (Fig. 2.1).
Other diseases associated with specific colours include lichen planus and dermatomyositis. Lichen planus has a well-known mauve hue, which is often helpful in
reaching a diagnosis. Dermatomyositis characteristically has the colour of the heliotrope flower associated with the periocular swelling that frequently occurs in this
disease (Fig. 2.2).
Measurement of the degree of erythema may be helpful in assessing the effects
of treatment on an erythematous skin disease. There are now two types of device
that can be used to do this, one is based on the comparator principle and the other
uses reflectance spectroscopy. Both employ complex electronics, are available commercially and are easy to use.
BROWN-BLACK PIGMENTATION
The degree of brown-black pigmentation depends on the activity of the pigmentproducing cells the melanocytes not on the number of cells. It also depends on
the size of the granules and the distribution of the pigment particles within the
epidermal cells. Shedding of the pigment from keratinocytes into the dermis is
known as pigmentary incontinence and causes a kind of tattooing, in which the
dusky pigment produced hangs on for many weeks or months.
Brown pigmentation is also caused by a breakdown product of blood
haemosiderin when this has leaked into the tissues (Fig. 2.3). It is very difficult to
tell this apart from melanin pigment, both clinically and histologically, but special
stains can help.
A brown-black discoloration of the skin over cartilaginous structures (ears and
nose) and, to a lesser extent, at other sites is seen in alcaptonuria, and is due to the
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as dry skin disorders. Water placed on scaling skin makes the surface temporarily
less scaly, but the scaling is not due to water deficiency.
As mentioned above, scaling is due to disturbances in keratinization, which
may be primary or secondary. In primary disorders of keratinization, a metabolic
abnormality prevents full and complete differentiation of the stratum corneum,
ending in the release of intact single keratinocytes. These disorders are generally
congenital in origin the ichthyoses being the best examples.
Scaling is also seen when keratinization is affected secondary to some other
pathological process affecting the epidermis. For example, the scaling seen in psoriasis and eczema is due to the inflammation that affects the epidermis in these
disorders. In psoriasis, and probably in some patients with chronic eczema, epidermal cell production is greatly increased and the rapid movement of the epidermal
cells upwards results in immature cells within the stratum corneum.
There are no simple ways to quantify scaling, although there are established
methods for assessing skin surface contour, in which the contour of skin surface
replicas is tracked with a very sensitive stylus and recorded electronically. Skin
surface contour may also be recorded optically by measuring the reflection of light
from the skin surface.
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(see page 100) are thickened and easily palpable and are called plaques. Sometimes,
lesions are very considerably proud of the skin and are known as nodules or
tumours. If the tumours are connected with the skin surface by a stalk, they are
said to be pedunculated. Nodules and pedunculated tumours are present in the
congenital condition called neurofibromatosis (Von Recklinghausens disease).
The edge of lesions can give some diagnostic help: well-defined edges are especially characteristic of psoriasis and ringworm. Characteristically, it is difficult to
discern where the abnormality ends in the eczematous disorders.
The shape of skin lesions can also help in diagnosis. Some skin disorders start off
as macular but clear in the centre, making ring-like or annular lesions. Ringworm,
granuloma annulare (see page 265) and erythema multiforme (see page 75) are
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three conditions in which the developed lesions tend to be annular (Figs 2.82.10).
Some skin disorders often produce oval lesions, pityriasis rosea being the best
example of this tendency. Occasionally, lesions assume bizarre patterns on the skin
surface that almost seem to be representing a particular pattern or symbol. This is
termed figurate, and many disorders, including psoriasis, may produce such lesions.
For the most part, skin lesions are not usually angular and do not form squares or
triangles. However, one condition, lichen planus (see page 144), does produce small
lesions that seem to have a roughly polygonal outline (Fig. 2.11).
In some instances, lesions such as plaques or tumours infiltrate into the substance of the skin and, in the case of such malignant lesions as basal cell carcinoma, squamous cell carcinoma or malignant melanoma, it is important to
recognize the presence of deep extensions of the lesion in order to plan treatment.
Clinically, it is possible for experienced observers to form some impression of the
degree of infiltration present by palpation, but this should be validated by histological support before any major surgical decision is made. There is some hope
that non-invasive assessment techniques such as ultrasound will be better able to
guide the surgeon than clinical examination alone.
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(a)
(b)
In eczema, oedema fluid collects within tiny cavities less than 1 mm in diameter
within the epidermis, known as vesicles (Fig. 2.13). Larger fluid-filled cavities are
called bullae (blisters). These may form due to fluid collecting beneath the epidermis (subepidermal), in which case their walls tend to be tough and the captured
blister fluid may be blood stained, or they may form by separation or breakdown
of epidermal cells (intraepidermal), when the walls tend to be thin, flaccid and
fragile. Subepidermal bullae form in bullous pemphigoid, dermatitis herpetiformis
and erythema multiforme. Intraepidermal bullae form in the different types of
pemphigus (see page 91) and herpes virus infections (see Figs 2.142.18).
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Secondary changes
An erosion is any breach of the epidermis. The term ulcer is used to denote a
broad, deep erosion that persists. Erosions may be covered by serous exudates or
crust; ulcers tend not to be covered.
Secondary changes
Secondary changes include:
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PRURITUS
Itching is the classic symptom of skin disorders, but it may occur in the apparent
absence of skin disease. Any skin abnormality can give rise to irritation, but some,
such as scabies, seem particularly able to cause severe pruritus. Most scabies
patients complain that their symptom of itch is much worse at night when they
get warm, but this is probably not specific to this disorder. Itching in atopic dermatitis, senile pruritus and senile xerosis is made worse by repeated bathing and
vigorous towelling afterwards, as well as by central heating and air conditioning
with low relative humidity. If pruritus is made worse by aspirin or food additives
such as tartrazine, sodium benzoate or the cinnamates, it is quite likely that
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urticaria is to blame. Persistent severe pruritus can be the most disabling and distressing symptom, which is quite difficult to relieve. Scratching provides partial
and transient relief from the symptom and it is fruitless to request that the patient
stop scratching. Scratching itself causes damage to the skin surface, which is visible as scratch marks (excoriations). In some patients, the repeated scratching and
rubbing cause lichenification and in others prurigo papules occur. Occasionally,
the scratch marks become infected. Uncommonly, the underlying disorder occurs
at the site of the injury from the scratch. This phenomenon is found in patients
with psoriasis and lichen planus and is known as the isomorphic response or the
Koebner phenomenon.
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find great difficulty in obtaining positions that require any kind of interpersonal
relationships.
Young patients with acne have particular problems because the disease is only
too visible, as it usually affects the face. Psoriasis quite often affects the hands, nails
and scalp margin, also causing difficulty for those whose occupations put them
into contact with the public.
Numerous other skin disorders put the affected individual at an economic and
social disadvantage. Vascular birthmarks and large neurofibromata are disfiguring
and tend to isolate the bearers. Chronic inflammatory facial disorders such as
rosacea and discoid lupus erythematosus also cause problems (Figs 2.22 and 2.23).
To summarize this point, individuals with visibly disordered skin are disabled
because of societys inherent avoidance reaction. One other aspect of this same
problem is the sufferers own perception of the impact they are making on all with
whom they come in contact. In most subjects who have persistent, unsightly skin
problems, the affected individuals become depressed and isolated. It is especially
damaging for those in their late teens and twenties who are desperately trying to
make relationships. Self-confidence is, in any case, not at a high point at this time in
their emotional development and a disfiguring skin disorder lowers their selfesteem incalculably. Many youngsters with acne and psoriasis find it difficult to conquer their embarrassment sufficiently to have girlfriends or boyfriends and that
aspect of their development may become stunted. It was once thought that many
skin disorders were caused by neurotic traits, stress and personality disorders. It is
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Summary
now increasingly appreciated that skin disorders often cause depression, anxiety and
stress, so that the wheel has turned full circle.
Skin disease can be enormously disabling when it affects the palms or soles.
Although the areas only occupy some 12 per cent of the bodys skin surface, disease of these sites may prevent walking and use of the hands for anything but
simple tasks, i.e. they are virtually completely disabled. Psoriasis and eczema are
the usual causes of this form of disablement because of the painful fissures that
tend to develop (Fig. 2.24). Patients with a severe atopic dermatitis may develop
similar painful fissures around the popliteal and antecubital fossae, so that limb
movements become extremely painful (Fig. 2.25). Those with severe congenital
disorders of keratinization are often severely troubled by this disordered mobility.
From what has been said so far, it will be appreciated that, contrary to popular
belief, patients with skin disorders are often appreciably disabled. They are
disabled on account of societys and their own reaction to the disease and because
of the physical limitations that the skin disease puts on them.
Skin disease infrequently kills, but often produces unhappiness, usually loss of
work and social deprivation as well as considerable physical discomfort.
Summary
Skin disorders may be generalized or localized to
lesions.
Normal-appearing skin may show structural or
functional abnormalities.
Skin colour is mainly determined by melanin
pigmentation and blood content, its oxygenation
and distribution. Particular shades of red may
indicate particular diseases, e.g. violaceous lichen
planus.
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C H A P T E R
26
27
29
Summary
35
As already mentioned, a major function of skin is its ability to protect the body from
the potentially injurious environment. All parts of the skin contribute to its role in
protection. The stratum corneum is a remarkably efcient barrier, protecting against
water loss to the environment and against the entry of toxic substances that the skin
may encounter. This same, thin structure also helps protect against solar ultraviolet
radiation (UVR), thermal injury and, to some extent, mechanical damage.
The vasculature is vital to the maintenance of a constant body temperature.
Vasodilatation and vasoconstriction allow loss and conservation of body heat,
respectively. The sweat glands, the hair and the subcutaneous fat are other parts
of the skin that assist in thermal homeostasis. Evaporation of sweat assists loss of
body heat, and the subcutaneous fat and hair help conserve heat because of their
insulating functions.
Melanin produced by melanocytes in the basal layer of the epidermis is
donated to the epidermal keratinocytes, which become corneocytes, and it is in
these that melanin absorbs solar UVR, providing essential protection to the skin
against damage from the suns rays. UVR stimulates melanin production, leading
to the well-known golden brown suntan and further protection.
We are subjected to a constant barrage of mechanical stimuli, which vary in
intensity, direction, area to which they are delivered and rate of delivery. The dermis contains a network of oriented, tough, collagenous bres, in the interstices of
which there is a viscid proteoglycan ground substance as well as elastic bres and
broblasts. Most of the mechanical response to physical stimuli is due to dermal
connective tissue. Overall, the mechanical properties can be described as viscoelastic. This means that skin extends in response to a linear force and will tend to
regain its original length after release of the force (elastic). It also ows and creeps
with some mechanical stimuli (viscous). Skin is also said to be anisotropic, as its
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mechanical properties vary according to the orientation of the body axis in which
the mechanical stimulus is delivered. The anisotropy results from the orientation
of the collagen bres, which vary according to site. Different resting tensions result
from the differing orientations and account for the development of broad and ugly
scars if incisions are made across the main orientation of the collagen bres rather
than parallel to it. Langers lines (made by joining the long axes of circular incisions
pulled by the internal forces over the skin surface) were an early attempt at revealing the resting tensions in skin. However, they did not take into account important
additional local considerations specic to each anatomical region.
The responses to mechanical stimuli vary according to the rate of delivery of the
stimulus, i.e. they are time dependent. They are also dependent on the stress history
of the anatomical part recent stress history being more important than distant.
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Agents that cause blistering are known as vesicants. Blister beetles release vesicants
(including cantharidin) when crushed on the skin. Colloquially known as Spanish
y, the substance, unjustiably, had the reputation of being an aphrodisiac.
Chemical warfare agents include vesicants known as the mustards, which crosslink DNA, preventing cell division, but also cause severe blistering and erosion on
contact with the skin.
Acneiform response
Some materials particularly irritate the hair follicles and stimulate the production
of sticky horn, causing comedos and an acneiform folliculitis (Fig. 3.3). Cocoa
butter, thick, oily materials including parafn waxes and substances such as isopropyl myristate are notorious for doing this in susceptible individuals. Cosmetics
were at one time often to blame, but now rarely have this effect because of rigorous safety testing. Lubricating and cutting oils may cause oil folliculitis or oil
acne in machine workers at skin sites that come into contact with the oil.
Some materials can injure melanocytes, causing depigmented patches that may
closely resemble vitiligo (see page 297). Substances used in the rubber industry
notably the additive paratertiary butyl phenol are notorious for causing such a
problem. Depigmentation may occur as a temporary phenomenon after irritant
dermatitis or other inammatory dermatoses. Hyperpigmentation can also follow
inammatory skin disease. This can be persistent as it results from the release of
melanin particles from injured keratinocytes, which are then engulfed by macrophages, resulting in a tattoo.
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VISIBLE LIGHT
700
600
500
ULTRAVIOLET RADIATION
400
320 280
185
subepidermal inammatory cell inltrate. Some 2 days after UVR injury, there is an
increase in the rate of melanin synthesis. It is probably not possible to stimulate a
tan without sustaining UVR-induced epidermal damage. Sunburn is easily recognized by the redness and, when severe, swelling and blistering as well. For some
unexplained reason, it is quite sharply restricted to the area of skin exposed. The
affected area is very sore and, if blistered and extensive, makes the individual feel
unwell and even require in-patient management as for a thermal burn.
An individuals sensitivity to solar UVR depends mostly on the degree of skin
pigmentation, but also to some extent on inherent metabolic factors. Sensitivity is
conventionally graded as follows in answer to the question Do you burn or tan in
the sun?
Type I
Type II
Type III
Type IV
Type V
Type VI
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EPIDERMAL DAMAGE
Minor degrees of epidermal abnormality, with variation in cell and nuclear size,
shape, staining and orientation, are known as dysplasia (or photodysplasia). They
are common and, although they are not detectable clinically, they may lead on to
pre-cancerous solar keratoses or Bowens disease, frankly invasive squamous or
basal cell carcinoma (see Chapter 13) and life-threatening malignant melanoma
(see Chapter 13).
DERMAL DAMAGE
Sun-damaged dermal connective tissue loses its brous quality and assumes a
homogenous, blob-like appearance in some sites and a chopped-up, short, stubby
bre appearance in others. When these occur together, they give a spaghetti and
meatball appearance. The degenerative change is termed solar elastosis as it stains
just like elastic tissue. Solar elastosis starts subepidermally, although separated
from the epidermis by a thin layer of normal dermis the grenz zone. With
increasing exposure, elastotic tissue extends deeper and deeper into the dermis.
Solar elastosis imparts a sallow, yellowish tint to affected skin and the altered
mechanical properties of the abnormal tissue are responsible for many of the
wrinkles and lines around the mouth and eyes on sun-damaged skin (Fig. 3.5).
Large telangiectatic blood vessels in the degenerate dermis account for the telangiectasia seen clinically (Fig. 3.6).
Topical retinoids (tretinoin, isotretinoin and tazarotene) used over several
months improve the appearance of photodamaged skin by stimulating the synthesis of new dermal connective tissue.
PREVENTION OF PHOTODAMAGE
Complete avoidance of sun exposure is very difcult to achieve and it is better to
aim at reducing the UVR dose as much as possible by:
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Sunscreens are creams or lotions that absorb and lter out or reect off the
damaging UVR. Older sunscreens contained substances such as the esters of
paraaminosalicylic acid, benzoic acid, the homosalicylates, the benzophenones
and the cinnamates, designed primarily to lter out the sunburning 290-nm UVB
segment, although some also gave a little protection in the UVA range. Newer
sunscreen constituents give protection against UVA as well and may be helpful in
protecting against chronic photodamage and skin cancer.
Sunscreen efcacy is usually quoted as a sun protection factor (SPF). The SPF
is the ratio of the minimal time of exposure to produce redness of the skin (in
minutes) with sunscreen protection compared to the minimal exposure time to
produce redness without sunscreen protection. For example, if it takes 15 minutes exposure to a standard UVR source to develop redness and only 1 minute to
develop redness without the sunscreen, the SPF of that sunscreen is 15. The test
has been carefully standardized so that one can place some condence in the SPF
as an indication of the protection against UVB.
It is more difcult to measure and express protection against UVA. In practice,
the protection against UVA provided by sunscreens is often expressed as a ratio of
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the protection against UVB to that offered to UVA in the star system, in which four
stars express the best ratio. There are two methods employed. One is the pigmentdarkening method, in which the time to the production of a transient darkening
of the skin is measured. The other method is an in vitro spectroscopic method.
Other important points concerning sun exposure include:
UVR is readily reected from whitish surfaces such as sand, snow and white
walls, and this increases the dose of UVR sustained.
A signicant amount of UVR diffuses through cloudy skies, and it is possible
to be burnt even on dull days.
The nearer the equator, the more direct the UVR and the easier it is to burn.
The higher the altitude of exposure, the greater the UVR exposure.
Lighter-skinned subjects are more at risk, i.e. ginger-haired or axen-haired,
blue-eyed, pink-skinned individuals who never tan and always burn (type I
subjects and, to a lesser extent, type II individuals). A Celtic ancestry, even in
comparatively darker-complexioned subjects, usually signies a marked sensitivity to solar UVR.
Skin can become sensitized to a specic part of the solar spectrum by chemical
agents that reach it either via the systemic route or after contacting the skin topically.
The molecule damages tissues after absorbing the UVR at a particular wavelength
Table 3.1 Skin diseases precipitated, caused or aggravated by sunlight
Disorder
Wavelengths responsible
Comment
Porphyrias
400 nm
Polymorphic light
eruption
Mostly the UV part of the spectrum, Papular or eczematous rash on exposed areas
but visible light may be involved
Actinic prurigo
Uncertain
Photosensitivities
Lupus erythematosus
Eczema/psoriasis
Unknown
Rosacea
Unknown
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Patients with this disorder start with severe photoallergic dermatitis and do not
respond to routine light avoidance. When photosensitivities are identied to plant
extracts or to antimicrobials such as trichlorosalicylanilide, avoidance does not
necessarily produce improvement. The skin of a few severely affected individuals
may be markedly thickened (Fig. 3.7) and may be involved on all sites not only
light exposed areas. The condition is then known as actinic reticuloid. Severely
affected patients need to be nursed in a darkened room to ensure complete protection from irradiation. Some improvement with azathioprine (50150 mg daily)
may be expected, but little else helps.
Polymorphic light eruption
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This occurs in girls and young women and looks somewhat like atopic dermatitis.
Conrmatory tests for the photodermatoses
Photopatch tests. Suspected photosensitizers are placed on the skin and irradiated with broad-spectrum UVR. Controls are run with irradiation alone and
with the suspected substances without irradiation. Patches are examined for
signs of eczema up to 72 hours after irradiation.
Photoprovocation tests. These specialized tests are only available at a few centres.
In one group of tests, the wavelength dependency (action spectrum) of the disorder is determined by shining monochromatic radiation (single wavelength)
on the skin using a monochromator.
Sweat rash
The term is quite non-specic and applied by the lay public to any disorder associated with sweating and the hot weather. Dermatoses as diverse as intertrigo and
folliculitis are sometimes known as sweat rashes.
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A common form of sweat rash is due to blockage of the sweat gland pores or
ducts near the surface with swollen over-hydrated horn. The term miliaria crystallina is applied to the tiny, thin walled vesicles that arise from blockage at the
pore near the surface. In miliaria rubra, red, inamed papules occur due to blockage lower in the duct. In miliaria profunda, the blockage is deep down and large
inammatory swellings develop. The most effective treatment is to cool the patient
with air conditioning and fans. Systemic antibiotics and anti-inammatory agents
may be required.
Dermatoses aggravated by solar exposure
Lupus erythematosus is very often aggravated by sun exposure, and patients with
this disease must not expose themselves to solar UVR. Rosacea is often, and atopic
dermatitis occasionally, made worse by the sun. Psoriasis and acne are mostly
improved by sun exposure, but some patients are, for some reason, made worse.
COLD INJURY
Frostbite is a form of acute tissue necrosis of ngers, toes, nose or ears due to coldinduced ischaemia.
Chilblains
Chilblains are common in the UK but rare elsewhere. They seem to occur in the
damp cold so often experienced in the UK and are also associated with subsequent warming. The lesions occur on the ngers, toes and occasionally elsewhere
as raised, dusky red or mauve swellings and are painful and/or itchy. They particularly affect plump young women, for some reason, as well as the elderly. Keeping
warm is the only effective treatment.
Raynauds phenomenon
Table 3.3 Some common
causes of Raynauds
phenomenon
Systemic sclerosis
Systemic lupus
erythematosus
Use of vibratory tools
Carpal tunnel syndrome
Cervical rib
Atherosclerosis
Polycythaemia rubra vera
In the majority of cases, no
precipitating cause can be found.
This common, curious response of the digital arteries to the cold is observed in
many disorders as well as occurring without any obvious underlying predisposing
condition (Table 3.3).
Classically, the ngers suddenly go a deathly white when exposed to the cold.
After a variable period, they go pink and then develop a bluish discoloration
the whole sequence lasting approximately 30 minutes. The condition is painful
and, during the winter, quite disabling. If severe, it can lead to atrophic changes
with loss of tissue and tapering of the ngers. Paronychial infection is a common
complication.
If no underlying cause can be found or the cause cannot be removed, symptomatic treatment directed towards keeping the hands warm and producing vasodilatation in them is needed. Electrically heated gloves, oral inositol nicotinate,
nifedipine (510 mg t.d.s.) and oxypentifylline (400 mg, two to three times daily)
may help individual patients.
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Summary
HEAT INJURY
Chronic heating causes injury to the skin, though this is not well characterized.
Infra red in the solar spectrum may play a role in chronic photodamage, but it is
difcult to determine what that role is. Chronic heat damage to the skin occurs on
the shins and elsewhere at sites habitually warmed by focal sources of heat a
condition known as erythema ab igne. Brownish-red reticulate pigmentation is
the dominant physical sign (Fig. 3.9), but keratoses and even squamous cell carcinoma can also occur at involved sites.
Summary
Damage to the skin may be caused by soaps,
detergents and oils that remove essential
constituents of the stratum corneum, allowing
penetration into and irritation of the epidermis.
Fair-skinned individuals are more susceptible to
injury from irritants.
Some agents, such as cocoa butter, irritate the hair
follicles in particular and cause an acne-like
response (comedogenic substances).
Toxic damage to melanocytes by some substances
causes areas of depigmentation.
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C H A P T E R
Skin
infections
Fungal disease of the skin
37
44
50
Summary
56
PITYRIASIS VERSICOLOR
This disorder is caused by the yeast-like micro-organism Pityrosporum ovale. This
microaerophilic, lipophilic denizen of the normal follicle only occasionally becomes
pathogenic when its growth is encouraged by heightened rates of sebum secretion
or there is depressed immunity.
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Skin infections
Clinically, pale, scaling macules develop insidiously over the skin of the chest
and back in young adults (Fig. 4.1), although, uncommonly, other sites can be
affected too (Fig. 4.2). Pale areas are left when the condition resolves. Diagnosis
is made by identication microscopically of grape-like clusters of spores and a meshwork of pseudomycelium in skin scrapings made more transparent by soaking the
scales for 20 minutes in 20 per cent potassium hydroxide. A more elegant and permanent preparation can be made using cyanoacrylate adhesive (crazy glue) to remove
a strip of supercial stratum corneum from the skin surface on a glass slide. The
slide is rolled off the skin after 20 seconds and then stained with periodic acidSchiff reagent (Fig. 4.3). This technique is known as skin surface biopsy. The skin
patches often uoresce an apple green in long-wave UVR (Woods light).
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Treatment
Tinea corporis
This is ringworm of the skin of the body or limbs. Pruntic, round or annular, red,
scaling, well-marginated patches are typical (Fig. 4.5). It has to be distinguished
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Skin infections
of erythema;
2 plantar, in which the sole is red and scaling; or
3 interdigital, in which the skin between the fourth and fth toes in particular is
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Tinea capitis
Ringworm of the scalp occurs in children exclusively and is mainly due to M. canis.
It invades the scalp stratum corneum and the hair cuticle (ectothrix infection),
causing pink, scaling patches on the scalp skin and areas of hair loss due to the
breakage of hair shafts (Fig. 4.7). It is easily spread by, for example, the sharing of
hairbrushes. Infected areas sometimes uoresce a light green under long-wave
UVR (the so-called Woods light).
In another variety of scalp ringworm caused by T. schoenleini, the fungus
invades the interior of the hair shaft (endothrix) and causes intense inammation
on the scalp, with swelling, pus formation and scalp scarring.
Tinea unguium
This condition is due to ringworm infection of the nail plate and the nail bed. The
fungi responsible are T. rubrum, T. metagrophytes or E. occosum. Infected nail
plates are discoloured yellowish or white and thickened (Fig. 4.8). Onycholysis
occurs and subungual debris collects (Fig. 4.8). The condition is much more common in the toenails than in the ngernails. Tinea unguium has to be distinguished
from psoriasis of the nails (see page 129).
(a)
(b)
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Skin infections
Case 3
Dai had been a miner for many years and felt that was the reason he had chronic
ringworm affecting his toenails and the soles of his feet. He was fed up with
having itchy, scaly feet and ugly, thickened toenails and sought treatment. Various
creams were prescribed but did not help. Eventually, a 3-month course of oral
terbinane began to clear the problem.
Tinea incognito
This is extensive ringworm with an atypical appearance due to the inappropriate use of topical corticosteroids (Fig. 4.9). The corticosteroids suppress the
protective inammatory response of the skin to the ringworm fungus, allowing it
to spread and altering its appearance.
Treatment
Griseofulvin (500 mg b.d.) is only active in ringworm infections and has a low
incidence of serious side effects.
Ketoconazole (200 mg daily) is active in both yeast and dermatophyte infections. This drug should be reserved for patients with severe and resistant
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These agents are administered for 26 weeks except for griseofulvin, which, when
given for tinea unguium of the toenails, may need to be given for 612 months.
Candidiasis (moniliasis, thrush)
This common infection is due to a yeast pathogen (Candida albicans) that resides
in the gastrointestinal tract as a commensal. It is a not infrequent cause of vulvovaginitis in pregnant women, in women taking oral contraceptives and in those
taking broad-spectrum antibiotics for acne. It is also responsible for some cases of
stomatitis in infants and the cause of infection of the gastrointestinal tract and
elsewhere in immunosuppressed people. It may contribute to the clinical picture
in the intertrigo seen in the body folds of the obese and in the napkin area in
infancy. Treatment with the imidazole preparations, topical and systemic, is effective. Oral and vaginal moniliasis responds to preparations of nystatin and
amiphenazole as well as to the imidazoles. Serious Candida infections respond to
systemic uconazole.
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Skin infections
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This is a diffuse, inammatory disorder of the subcutis and skin caused by several
different micro-organisms and is of variable severity.
It is relatively common, particularly on the limbs, and often occurs on legs
affected by venous ulceration or by lymphoedema. There is pain, tenderness,
slight swelling and a variable degree of diffuse erythema.
Broad-spectrum antibiotics are indicated, as the micro-organisms may be
Gram negative in type (e.g. Escherichia coli) or Gram positive. Cephradine and
ucloxacillin (250 mg of each 6-hourly) are one suitable combination.
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Skin infections
ANTHRAX
Anthrax is due to a rare, potentially fatal infection with a Gram-positive bacillus
(Bacillus anthracis) causing black, scabbed sores and septicaemia. It is spread by
farm animals and, because the micro-organism has a resistant spore form, can
stay on infected land for years. It has assumed a major importance because of its
deliberate spread by terrorists in the USA.
TUBERCULOSIS
Tuberculosis is a multi-system disease caused by varieties of the waxy-enveloped
bacterium Mycobacterium tuberculosis. Several types of skin tuberculosis were once
commonly seen, but are now quite rare in developed countries. However, tuberculosis is, unfortunately, now once again becoming quite common because of the
appearance and spread of AIDS. The bacillus can be cultured in special media in
vitro, but grows very slowly. Special stains are needed to detect it in tissue.
LUPUS VULGARIS
Lupus vulgaris is a rare disorder causing a slowly progressive, granulomatous
plaque on the skin caused by the tubercle bacillus. It slowly increases in size, over
one, two or three decades. It often has a thickened psoriasiform appearance, but
blanching with a glass microscope slide (diascopy) will reveal grey-green foci
(apple jelly nodules) due to the underlying granulomatous inammation.
Treatment is initially with triple therapy of rifampicin, pyrazinamide and isoniazid over a 2-month period, followed by a continuation treatment phase with
isoniazid and pyrazinamide.
Tuberculosis verrucosa cutis (warty tuberculosis)
This is seen on the backs of the hands, knees, elbows and buttocks whenever abrasive contact with the earth and expectorated tubercle bacilli has been made.
Thickened, warty plaques are present, which are sometimes misdiagnosed as
viral warts. Diagnosis is conrmed by biopsy showing tuberculoid granulomata
and caseation necrosis.
Treatment is as for lupus vulgaris.
Other forms of cutaneous tuberculosis
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Mycobacterium marinum, which lives in water, is sometimes caught from swimming pools and sh tanks. It has a 3-week incubation period and causes plaques,
abscesses and erosions on the elbows and knees in particular.
The condition responds to minocycline or a trimethoprimsulphamethoxazole
combination.
Buruli ulcer
SARCOIDOSIS
Recent data suggest that the disorder is, in many patients, an unusual reaction to
M. tuberculosis. Sarcoidosis is a multi-system disease with manifestations in the
respiratory system, the reticuloendothelial system and the skin and occasionally
in the bony skeleton and central nervous and cardiovascular systems. In the skin,
one of the most common varieties consists of multiple, reddish purple papules
(Fig. 4.12). Deeper nodules and plaques are also seen, as are bluish chilblain-like
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Skin infections
swellings of the ngers, nose and ears (lupus pernio). These types are inltrated
by typical sarcoid tissue (see below), but another manifestation, erythema
nodosum (see page 77), is not.
Histologically, the typical lesion is the naked tubercle, which contains foci of
macrophages and giant cells without many surrounding lymphocytes.
Treatment may not be required if the lesions are not troublesome, as they are
self-healing, but when large they may leave scarring. For these large lesions,
systemic corticosteroids or non-steroidal anti-inammatory agents may be
required.
The pattern of involvement is much dependent on the immune status of the individual. The two extremes are the lepromatous form seen in anergic individuals
and the tuberculoid form seen in individuals with a high resistance. Because there
are many gradations between these polar types, the range of clinical signs and the
corresponding nomenclature have become very complicated. Where the changes
are near tuberculoid, the term borderline tuberculoid is used; similarly borderline lepromatous is used for lesions that are close to the other type. Dimorphic
refers to both types of lesion being present. In tuberculoid lesions, nerves are
infected, which become thickened. The affected areas are well dened, macular
and hypopigmented, as well as being anaesthetic because of the nerve involvement. The anaesthesia results in injury, deformity and disability. In lepromatous
leprosy, the infection is much more extensive, with thickening of the affected
tissue as well as surface changes, with some hypopigmentation. On the face, the
thickening gives rise to the characteristic leonine facies, with accentuation of the
soft tissues of the nose and supraorbital areas. Where there is resistance, few
bacteria can be detected in the lesions (paucibacillary types of leprosy). Types
in which many bacteria are found and the patients are anergic are known as
multibacillary.
In general, the disease can produce dreadful deformity and disability unless
skilfully treated, and it still evokes great fear in primitive communities. Because
the disorder causes patchy hypopigmentation, the differential diagnosis includes
vitiligo pityriasis versicolor and pityriasis alba.
In tuberculoid types, there is a striking granulomatous inammation with
many giant cells and only a few M. leprae to be found. In the lepromatous types,
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there are many macrophages that are stuffed with M. leprae (causing the appearance of foamy macrophages).
Treatment
The treatment of choice is with dapsone (100 mg daily, for periods of a minimum
of 6 months) with rifampicin (600 mg monthly) for paucibacillary types of leprosy. During treatment, the patients condition may are and deteriorate, causing
curious appearances in some, including erythema nodosum-like and ichthyosislike reactions. Multibacillary types should also be treated with dapsone (100 mg
daily) and in addition rifampicin (600 mg once monthly) and clofazimine (50 mg
daily). Drug resistance is becoming a major problem.
LYME DISEASE
Lyme disease is caused by the Borrelia burgdori micro-organism, which is spread
by the bite of a tick and has been described in several areas of Europe, including
the UK, and in the USA. The disorder is multi-system in that there may be
arthropathy, cardiovascular and central nervous components, as well as systemic
upset. The skin may be involved in the early stages and show an erythematous ring
that expands outwards (erythema chronicum migrans). Later, skin atrophy may
be seen (acrodermatitis chronica atrophicans), or brosis in a morphoea-like
condition. Diagnosis is made by identication of the organism in the tissues or by
detection of antibodies in the blood.
Treatment is with antibiotics preferably penicillin.
LEISHMANIASIS
The term refers to a group of diseases caused by a genus of closely related protozoal parasites with complex life cycles, which include time spent in small rodents.
These diseases are spread by biting arthropods (mostly sandies) in tropical and
subtropical areas. Some forms cause severe systemic disease and are prevalent in
some areas of Africa and South America and the Indian subcontinent: Others
cause predominantly cutaneous or mucocutaneous disease.
Cutaneous forms are found around the Mediterranean littoral and North Africa
and in South America. The Mediterranean type is caused by Leishmania major
and L. tropica. After an incubation period of about 2 months, a boil-like lesion
appears, usually on an exposed site (Baghdad boil). Later, this breaks down
to produce a sloughy ulcer (oriental sore: Fig. 4.13), which persists for some
months before healing spontaneously, with scarring and the development of
immunity.
Mucocutaneous forms occur mainly in South America (New World leishmaniasis)
and are due to L. mexicana and L. brasiliensis. Small ulcers develop (Chicleros
ulcer) that seem more destructive than the Old World types but also more
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Skin infections
persistent, and later in the disease destructive lesions appear, affecting nasal
mucosa in about half of the patients.
A cutaneous component to visceral forms is less common, but more extensive,
and includes a diffuse cutaneous form with many plaques and nodules resembling
lepromatous leprosy, a recidivans form with persistent plaques resembling lupus
vulgaris, and post kala-azar (dermal leishmaniasis), occurring after the visceral
disease and marked by the appearance of numerous small papules.
Biopsy shows mixed granulomatous inammation. The parasites can be identied by special stains and can also be cultured in specialized media. There is also
an intracutaneous skin test (leishmanin), which becomes inamed after injection
in most patients.
Treatment
The localized small ulcers heal spontaneously, but can be treated by freezing or
curettage. Inltration with sodium stibogluconate has been used. Systemic sodium
stibogluconate or pentamidine may also be used for severe and resistant cases.
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because the disorder is often precipitated by minor pyrexial disorders. It may also
be precipitated by sun exposure. Commonly, the lesions occur around the mouth
or on the lip. They start as grouped, tender and/or painful papules or papulovesicles (Fig. 4.14) and then coalesce to form a crusted erosion. The sequence takes
some 714 days from initial discomfort to the nal pink macule marking where
lesions have been.
Genital herpes affects the glans penis and the shaft of the penis. In women, the
vulval region or labia minora is usually involved, but lesions may occur elsewhere
on the buttocks or mons pubis. It may occur cyclically with the menses.
The disorder is caught venereally and has become extremely common. It is
painful and inhibits sexual activity.
The vesicle results from epidermal cell degeneration, and smears taken from
the lesion showing degenerate cells may help in diagnosis. The diagnosis can also
be made by identifying the virus using an immunouorescent method with antibodies to the herpes virus.
Treatment
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Skin infections
VARICELLA
This common childhood ailment is spread by droplets and debris from the lesions
and has an incubation period of 1421 days. There is accompanying fever and
malaise. Lesions are common on the face and trunk, but less common on the
limbs. Papules and papulovesicles become crusted, the crust dropping off after
some 714 days, leaving pock-type scars in many instances.
(a)
(b)
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to suffer from pain and paraesthesiae in the area long after the skin lesions have
disappeared.
Herpes zoster may occur where there is immunosuppression, as in AIDS or a
lymphoma. When this occurs, the disorder is often very severe and may involve
several dermatomes.
For most people, no specic treatment is required apart from keeping the
lesions clean and, if necessary, the application of antimicrobial preparations to
prevent or combat secondary infection. The drug aciclovir, administered by
mouth in a dose of 800 mg ve times daily (or by infusion) on day 1 of the disorder, shortens the disease and decreases its severity.
VIRAL WARTS
Warts are caused by a member of the human papillomavirus family, of which
there are many antigenic types (Table 4.1). Particular clinical types of wart are
caused by particular antigenic types. It is likely that they are caught by direct
contact of skin with wart virus-containing horny debris. Genital warts are caught
mostly (but not exclusively) by venereal contact. Some perianal warts may be
transmitted by homosexual contact or by child abuse.
The different varieties are illustrated in Figure 4.16. There are usually little
black dots near the surface of the wart, representing thrombosed capillaries in
elongated dermal papillae.
Plantar warts are painful, some warts are irritating, and all warts are unsightly
and aggravating. They are a particular problem in immunosuppressed patients.
In one congenital condition, plane warts spread extensively on the arms, face, trunk
Table 4.1 Human papillomavirus (HPV) types and the common clinical varieties of
warts with which they are associated
Clinical type
2, 4
Plane warts
3, 10
Mosaic warts
Epidermodysplasia verruciformis
Laryngeal papilloma
6, 11
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(a)
(b)
(d)
(e)
(c)
Figure 4.16 (a) Typical viral warts of nger. (b) Large paronychial viral wart. (c) Mosaic wart. (d) Perineal warts in an
adult. (e) Multiple penile warts.
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and limbs and some lesions can transform to squamous cell carcinoma. This rare
disorder, known as epidermodysplasia verruciformis, seems to have its basis in a
disorder of delayed hypersensitivity.
There is epidermal thickening, with particular increase in the granular cell
layer, which also shows a characteristic basophilic stippled appearance (Fig. 4.17).
All warts disappear spontaneously, but may persist for many months or some
years. Treatment is, in general, not very satisfactory and relies on some form of
local tissue destruction. The techniques mostly used are cryotherapy (tissue freezing with liquid nitrogen or solid carbon dioxide), curettage and cautery or chemical destruction with topical preparations containing salicylic acid, lactic acid,
podophyllin or glutaraldehyde. Popular preparations contain high concentrations
of salicylic acid (1220 per cent) and lactic acid (420 per cent) or podophyllin (up
to 15 per cent). Podophyllin is a plant extract containing potent cytotoxic alkaloids,
one of which, podophyllotoxin, is also available as a pure preparation (0.5 per
cent). Other methods that have been used include intracutaneous injections of
cytotoxics such as bleomycin and injections of recombinant interferon.
MOLLUSCUM CONTAGIOSUM
Molluscum contagiosum is a common infection of the skin caused by a virus of
the pox virus group. It is transmitted by skin-to-skin contact.
The typical molluscum lesion is a pink-coloured or skin-coloured, umbilicated
papule containing a greyish central plug (Fig. 4.18). There may be one or many
lesions. The face and genital regions are commonly involved.
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Skin infections
Pathology
Summary
The normal ora of the skin consists of
Gram-positive cocci (Staphylococcus epidermidis)
Gram-positive rods (Propionibacterium acnes)
and Gram-positive yeasts (Pityrosporum ovale).
Pityriasis versicolor is caused by Pityrosporum ovale
when there is depressed immunity or when there is
heightened sebum secretion. Fawn, scaling macules
occur over the trunk. Treatments with imidazole
creams or itraconazole by mouth are effective.
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Summary
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C H A P T E R
58
Pediculosis
63
65
69
Summary
70
The way that the skin reacts to the hostile attentions of arthropods and small
invertebrates depends partly on the extent and severity of the attack and particularly on the immune status of the individual attacked.
Each geographical region has its own spectrum of skin problems due to the local
fauna. Although some disorders, such as scabies, are the same the world over, the
pattern and incidence of infestations and bites differ markedly from place to place.
In general, the extent of skin problems due to arthropods is directly related to
the sophistication and wealth of the society in question, because of the effects of
personal hygiene, education, effective waste disposal and prophylaxis.
Scabies
Scabies is due to infestation with the human scabies mite (Acarus hominis,
Sarcoptes scabiei). The mite is an obligate parasite and has no separate existence
off the human body.
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Scabies
burrows. This generally does not happen before 1 month after the initial invasion
of the mite; subsequent infestations cause symptoms and signs within a few days
as the individual is already sensitized.
Infestation occurs after close skin-to-skin contact with an infested individual,
sexual contact being the most frequent but not the only cause of infestation.
There have been several notable pandemics of scabies in recent history. The
most recent of these started in the mid-1960s and ended in the early 1970s,
although between peaks of incidence the disorder continues to appear sporadically
and in localized mini-epidemics such as within families or in nursing homes.
CLINICAL FEATURES
The disorder is notorious for the intensity of itch that it causes, even in the presence of relatively minor physical signs. The physical signs are essentially those
of eczema and the effects of scratching. Vesicles are seen, but excoriations and
prurigo-like papules are more common (Figs 5.1 and 5.2). Scaling, oozing and
crusting can also be present in some sites due to secondary infection. However, the
primary lesion is that of the scabies burrow or run, which is a tiny, raised, linear
or serpiginous white mark (Fig. 5.3).
The favourite sites for lesions are portrayed in Figure 5.4. It is odd that they
should be symmetrical and concentrated in certain sites consistently. The best
sites on which to nd scabies burrows are the palms and the interdigital areas of
the ngers, the exural creases and over the elbows. Scabies lesions also commonly occur around the anterior axillary fold, the areolae of the breast, the buttock folds, lower abdomen, genitalia, knees, ankles and soles. Lesions are observed
on the head and neck in infants only.
The severity of the eruption depends on the number of mites present and this
is mostly dependent on the immune status of the individual. In severely immunosuppressed individuals, such as those with human immunodeciency virus (HIV)
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(a)
(b)
DIAGNOSIS
The diagnosis of scabies is not always easy, but is much helped by nding the burrows of the female scabies mite, which are pathognomonic of the disease and their
recognition is important. The burrows are grey-white, linear, slightly raised
marks, some 14 mm long, and are present on the favoured sites. The number of
burrows present is variable myriads in severe infestations in the elderly, but few
in the fastidiously hygienic young.
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Scabies
Finding the mite (or its eggs) by using a pin or by examining skin scrapings
(Fig. 5.6) or a skin surface biopsy taken with cyanoacrylate glue conrms the diagnosis (Fig. 5.7).
Identication of the telltale burrows or mite is not always easy, even for the
experienced! For the 20 per cent of scabies patients in the UK in whom burrows
cannot be identied, a positive family or social history with itching contacts is
helpful evidence and, in the presence of a compatible clinical picture, treatment
should be instituted. Differential diagnosis is set out in Table 5.1.
TREATMENT
Treatment should be instituted as soon as the diagnosis has been made to prevent
the infestation spreading. It should also be offered to everyone who lives with the
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Comment
Canine scabies
Eczematous diseases
Dermatitis herpetiformis
Mechanical irritation by
breglass
Pediculosis
Percentage
Comment
Malathion
0.5
Permethrin
1.0
Crotamiton
10.0
Monosulram
25.0
patient and to all other sexual contacts, who should use the treatment at the same
time as the patient.
The treatments employed are applied to the whole skin surface apart from
the head and neck, and are for this reason usually lotions, although creams are
also sometimes used. The patient should be instructed to have a hot bath before
applying the treatment, after which no further application or bathing is permitted
for 24 hours. The particular agents used are set out in Table 5.2.
Case 4
Sydney was 35 and began to itch all over two weeks ago. Now his girlfriend was
also itching, as were her mother and brother. Close inspection of the skin showed
many excoriations. Over the buttocks and genitalia there were papules and tiny,
whitish lines, at the end of which there were minute black specks. Microscopy of
these showed them to be scabies mites. Sydney was given permethrin lotion and
told to use it all over from the neck down after a hot bath. His girlfriend and her
family were also given the treatment. Improvement in the itching started some
2 weeks later.
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Pediculosis
DOG SCABIES
The mite causing dog scabies is similar to that causing human scabies, but the dog
scabies mite does not cause the same clinical picture as human scabies. The rash
only occurs at the site on the skin with which the dog has been in contact and does
not spread to other areas. Scabies burrows are not found. The correct treatment is
to treat the dog and to give any topical anti-itch preparation to the patient for the
affected site.
Pediculosis
Pediculosis is the result of infestation with one of the varieties of the human louse.
The different varieties cause different patterns of infestation.
Itching is the predominant complaint. The scratching that results can cause secondary infection with exudation and crusting, but if this does not occur, all that
may be seen are excoriation and red papules on the skin surface.
Examination of the hair will reveal the louse eggs (nits) stuck to the hair shaft
(Fig. 5.8). Careful inspection will also detect the adult louse itself, which is less
than 1 mm long and greyish or, after feeding, reddish in hue. When it moves it
deserves the description of mobile dandruff .
Conrmation of the diagnosis is the microscopic identication of the louse
(Fig. 5.9) or the nits stuck to the hair shafts.
Treatment
The pediculicides used are set out in Table 5.3. The recommended regimen is
application to the scalp of malathion or carbaryl lotion for a 12-hour period, followed by shampooing with shampoo containing the same pediculicide. Care must
be taken to ensure that all close friends and family are also treated. A further treatment 1 month later is also necessary to kill off all the young lice that may have
hatched from nits that remained alive after the initial treatment.
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Percentage
Comment
Malathion
Carbaryl
Phenothrin
0.5
0.5
0.2
Itching without a great deal to see to account for the symptom is usual in the early
stages. Some excoriations, blood crusts and bluish marks on the skin where the
louse has fed may also be seen. Later in the disease, lichenication and eczema
complete the picture of vagabonds disease.
Treatment
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Treatment
One of the pediculicides in Table 5.3 should be used, with a repeat treatment after
1 month. Shaving of pubic hair is sometimes advised, but is not really necessary.
All sexual contacts should be treated.
MOSQUITOES
Mosquito bites tend to be on exposed areas. Some varieties of mosquito (e.g. the
culicine mosquitoes) can cause blisters when they bite. The bites may be extremely
itchy and prominent (Fig. 5.11) and may become infected after being scratched.
FLEAS
Flea bites are mainly sustained from cat and dog eas, which occasionally
temporarily visit a human host. They drop off their original hosts and live on
carpets and rugs, as do their young, and jump up when they feel the vibration of
footsteps. The bites, which are small and itchy, are often, but not exclusively, on
the legs.
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Arthropod
Micro-organism
Malaria
Mosquitoes
(Anopheles species)
Malaria parasite a
(Plasmodium species)
Trypanosomiasis
(sleeping sickness)
Tsetse y
Trypanosoma brucei a
Leishmaniasis
Visceral
Cutaneous
Mucocutaneous
Sandy
(Phlebotomus species)
Onchocerciasis
Blacky
(Similium species)
Onchocerca volvulus b
Bubonic plague
Rat ea
Pasteurella pestis c
Leishmania donovani a
Leishmania tropica a
Leishmania braziliensis a
Protozoon.
Thread-like nematode worm.
c
Bacterium.
b
Arthropod
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TICKS
Ticks stay stuck to the skin for some time after biting and are found mainly in
agricultural communities, as the principal host is mostly sheep.
MITES
A large variety of mites may occasionally bite humans. Most of these, such as bird
mites or Cheyletellia mites living on cats, dogs and rabbits (amongst others), cause
small, red, itchy papules and are quite difcult to identify (Fig. 5.12).
PAPULAR URTICARIA
Papular urticaria is a term used to describe a recurrent, disseminated, itchy papular eruption due to either insect bites or hypersensitivity to them.
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Diagnosis
The lesions themselves should be compatible, i.e. they should be papules or, less
commonly, blisters, and it helps if puncture marks can be found in the lesion. It is
commonplace for the patients (or their parents) to deny the possibility of insect
bites being responsible for the lesions, as there seems to be a social stigma attached
to being the recipient of them. A detailed history is necessary, with particular
attention being given to the presence of domestic animals, proximity to farms,
the occurrence of similar lesions in other family members, and the periodicity of
lesions.
Biopsy may occasionally be helpful in that it may well rule out other disorders.
The presence of a mixed inammatory cell inltrate in the upper and mid
dermis is typical, but the pattern and density of cellular inltrate are variable
(Fig. 5.13).
Searching for the biting arthropod in the home may be fruitless unless the
assistance of trained personnel is sought. Examination of brushings from the
coats of dogs by veterinarians may be successful in identifying the culprit
cheyletellia, for example.
Treatment
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due to the liberation of toxic products from the dying microlariae. Hetrazan has
no effect on the adult worm and it is necessary to treat with the potentially toxic
drug Suramin to kill off the worm and prevent further production of microlariae. Ivermectin is also helpful.
Summary
Scabies is caused by a tiny mite, the female of
which burrows into the stratum corneum. It is
extremely itchy and is caught by skin contact with
an infected individual.
The primary lesion is the scabies run or burrow,
at the end of which sits the mite. Excoriated papules
and vesicles are also seen. Affected sites include
palms, soles, knees, elbow, ankles and genitalia.
Heavy infestation occurs in immunocompromised
individuals, resulting in thick, crusted areas known
as Norwegian scabies.
Treatment is with permethrin or malathion, which
should be applied over the entire skin surface below
the neck after a bath and be used for all human
contacts.
Pediculosis is caused by infestation with the human
louse. Head lice (Pediculus capitis) cause
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C H A P T E R
Immunologically
mediated skin disorders
Urticaria and angioedema
71
Erythema multiforme
75
Erythema nodosum
77
Annular erythemas
77
Autoimmune disorders
77
Systemic sclerosis
80
Morphoea
82
Dermatomyositis
83
84
Blistering diseases
87
Dermatitis herpetiformis
89
Epidermolysis bullosa
90
Pemphigus
91
Drug eruptions
92
Summary
95
CLINICAL FEATURES
Urticaria is extremely common (nettlerash, weals and hives are popular names
for this disorder) and there are few individuals who do not experience it in one
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form or another during their lifetime. Urticarial lesions are itchy, red papules
and plaques of variable size (Fig. 6.1) that arise suddenly, often within a few minutes, and last 624 hours. They may assume odd, polycyclic, annular and geographic forms.
An important characteristic of urticaria is its transience, but very occasionally
urticarial lesions stay for days rather than hours and leave a brownish stain. This
type of urticaria is due to involvement of small blood vessels and is known as urticarial vasculitis.
In many patients with urticaria and in a few people without it, rm pressure
over a track with a blunt object such as a key over the skin of the back will produce blanching, then redness, then a weal. This phenomenon, which is an exaggeration of the normal triple response, causes itching and is known as
dermographism.
In angioedema, the lesions are deeper and the swelling much more extensive
than in urticaria (Fig. 6.2). Angioedema may accompany urticaria or may occur
independently. The face and the tissues of the oropharynx are sometimes affected
by the angioedema, which can lead to life-threatening difculties in swallowing
and breathing.
Urticaria and angioedema can last for a few days or some years. A common
pattern is for the disorder to recur in a series of attacks. Chronic urticaria is a
common and sometimes disabling disorder, which in most cases is of unknown
origin.
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CAUSES
The ultimate cause of urticaria and angioedema is release of histamine from mast
cell granules, but there is a large number of stimuli that can do this. Many are
immunological, some are purely pharmacological and others are physical. Type I
immunological reactions are involved in the production of urticarial lesions. Table
6.1 gives some of the known causes. Although the cause(s) of urticaria can be identied in some patients, in many it remains a mystery. In recent years it has been
found that some patients have antibodies to receptors on their own mast cells.
Urticarial swelling of the hands, face and elsewhere may occur after exposure to the
cold. The reaction can be elicited by an ice block (Fig. 6.3). There is a familial form.
Pressure urticaria
Urticarial lesions develop some time (up to several hours) after pressure on the
skin, for example from belts or other tight clothing, or from the rungs of a ladder.
Dermographism
Many patients with urticaria mark easily when their skin is rubbed rmly, for
example with a key. This is an exaggerated triple response and is quite troublesome to some patients (Fig. 6.4).
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Solar urticaria
Urticarial spots develop on exposed skin a few minutes after exposure to the sun.
Various wavelengths may be responsible (Fig. 6.5).
CHOLINERGIC URTICARIA
Irritating, small urticarial spots develop after exercise or hot baths stimuli that
evoke sweating from the post-ganglionic cholinergically enervated sweat glands.
This very common disorder can be very disabling in a few patients, as it effectively
prevents them doing any kind of physical activity.
DRUG-INDUCED URTICARIA
Penicillin hypersensitivity is a common cause of urticaria. Attacks vary from the
life-threatening acute anaphylactic type to crops of small urticarial papules.
Opioid drugs can cause urticaria by directly stimulating histamine release. Up to
one-third of patients with urticaria develop lesions after challenge with aspirin,
but whether this is entirely due to pharmacological stimulation of histamine
release, involvement in prostanoid metabolism, or hypersensitivity is not certain.
STINGS
Nettles, jellysh tentacles and some insect stings elicit histamine release at the site
of skin contact, producing painful local reactions. Urticaria can also be a sign of
an underlying systemic disorder such as lupus erythematosus and amyloidosis
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Erythema multiforme
and a component of disorders such as dermatitis herpetiformis (see page 89) and
allergic vasculitis (see page 84).
Treatment
Erythema multiforme
DEFINITION
An acute and relatively short-lived inammatory reaction of skin and mucosae,
occurring in response to a variety of antigenic stimuli and resulting in scattered
lesions at the dermoepidermal junction.
CLINICAL FEATURES
Individual lesions are red to purple maculopapules, some of which become annular or target-like and may blister (Figs 6.6 and 6.7). The face and upper limbs are
preferentially involved, and the buccal mucosa is often involved in severely
affected patients. In the worst cases, there is severe systemic upset. The front of the
mouth is eroded in severely affected patients (Fig. 6.8). The conjunctivae and genital mucosae are affected in a few. The disorder starts acutely and usually lasts less
than 2 weeks, although crops of new lesions often develop in the rst few days.
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The disorder may be precipitated by infections, including herpes simplex, orf, coccidioidomycosis and histoplasmosis, drugs such as piroxicam, indomethacin and
other non-steroidal anti-inammatory compounds, sulphonamides and thiazide
diuretics (Table 6.2). In a proportion of patients, it recurs for no very obvious reason.
Mononuclear inammatory cells collect at the dermoepidermal junction and
uid collects beneath the epidermis.
Psychotropic drugs
Sulphonamides, other
antimicrobial drugs
Infections
Herpes simplex
TREATMENT
The disorder is self-limiting and only symptomatic treatment is required. Where
there is serious systemic disturbance, systemic steroids may be given.
Orf
Mycoplasma
Histoplasmosis
Coccidioidomycosis
Ultraviolet irradiation
Ulcerative colitis and
Crohns disease
Case 5
The condition started with soreness in the mouth. Sally, aged 27, thought that is
was the curry she had had the previous night. Within 2 days, she had developed
a widespread rash particularly over her arms and upper trunk. Many of the
lesions were annular and some showed blistering. The rash began to improve
after 12 days, but the disorder had made her feel tired and ill. It was thought to
be erythema multiforme in all likelihood precipitated by an attack of labial
herpes simplex some 2 weeks before the onset.
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Autoimmune disorders
Erythema nodosum
DEFINITION
A painful inammatory disorder in which crops of tender nodules occur in
response to antigenic stimuli.
CLINICAL FEATURES
Individual lesions are red, raised and tender and vary in size from 1 to 3 cm in
diameter. They occur in crops on the shins (Fig. 6.9) and, less commonly, on the
forearms. There may be malaise, fever and an accompanying arthralgia of the
ankles. The lesions take 26 weeks to resolve and leave a bruised appearance.
Crops of lesions may develop over some months.
TREATMENT
Tuberculosis
Sarcoidosis
Brucellosis
Annular erythemas
There are several disorders that are marked by the appearance of erythematous
rings, which usually gradually enlarge and then disappear. Generally their signicance is uncertain, but one, known as erythema gyratum repens, signies the
presence of an underlying visceral neoplasm (see page 281) and another, erythema chronicum migrans, indicates the presence of Lyme disease.
Leprosy
Autoimmune disorders
These disorders are also known as the collagen vascular disorders and the connective tissue diseases. In general terms, the immune system of an individual with
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autoimmune disease fails to recognize the individuals own tissues and mounts
an attack on them. In most of the disorders in this group, the inammatory
process seems to involve the small blood vessels in particular (vasculitis).
LUPUS ERYTHEMATOSUS
This is divided into systemic and cutaneous forms, although there is some overlap.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) often involves the skin as well as many other
organ systems, but in one type of SLE subacute SLE the skin is prominently
affected. Antibodies to nuclear DNA occur in 8090 per cent of patients with SLE
and antibodies to other nuclear components are present in subgroups of patients.
These antinuclear factors may be intimately involved in the pathogenesis of the
disease.
Common components of SLE include a rheumatoid-like arthropathy, a
glomerulonephritis, inammatory disorder of the pulmonary and cardiovascular
systems, a polyserositis, central nervous system involvement and skin disorder.
The skin components of SLE include facial erythema across the cheeks and nose
(buttery erythema: Fig. 6.10), and discoid lupus erythematosus (DLE) occurs in
the pure cutaneous form.
Mainly young women are affected. The 5-year mortality has been variously
estimated to be between 15 and 50 per cent, dependent on the organ systems
affected and the pace of the disease.
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Autoimmune disorders
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Pathology
The changes are similar to those described for SLE, but the epidermal degenerative changes are more marked, with scattered cytoid body formation and patchy
epidermal atrophy and thickening.
Treatment
Sun avoidance and use of sunscreens are important. Individual lesions sometimes
respond to potent topical corticosteroids. Where these do not cope with the disease, hydroxychloroquine (200400 mg per day) is often helpful. Caution must
be exercised concerning the possible, although rare, toxic effects of this drug on
the retina. Systemic steroids, the oral gold compound auranon, cyclosporin and
acitretin are other drugs that have been used successfully.
Systemic sclerosis
Scleroderma is an important component of systemic sclerosis. In this autoimmune disorder, the broblast is stimulated to produce new collagen. When other
organ systems are involved, the disorder affects the vasculature as well as broblasts, and Raynauds phenomenon, renal involvement with glomerular disease,
gut involvement with dysphagia and gut hypomobility, a rheumatoid type of
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Systemic sclerosis
polyarthropathy and skin stiffening are all seen (Table 6.4). As with SLE, the
disease is mostly seen in young women, and the pace of the disorder is extremely
variable. It may start insidiously over some months or even years, with progressively worsening Raynauds phenomenon and gradual thickening and stiffening of
the skin of the hands and face. This causes a characteristic beak-like facial appearance, with narrowing of the mouth (Fig. 6.14). Telangiectatic macules appear over
the face (Fig. 6.15) and deposits of calcium develop in the skin. The term CRST
syndrome is used for this constellation of problems (calcinosis cutis, Raynauds
sclerosis and telangiectasia). When there is also dysphagia due to oesophageal
involvement, the term CREST is more appropriate.
In more rapidly progressive systemic sclerosis, there may be more serious vascular disease affecting the ngers, resulting in tissue necrosis and even the loss of
portions of the digits. Renal or pulmonary disease may eventually cause the death
of the patient the 5-year mortality rate of this disease being 30 per cent or more.
Biopsy of affected skin shows excess new collagen that has an eosinophilic and
almost homogeneous appearance. Antinuclear antibodies occur in up to 30 per cent
of patients.
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TREATMENT
There is no reliable way of signicantly modifying the disorder. Some improvement can be obtained by skilful management of the Raynauds phenomenon, and
occasionally with penicillamine and immunosuppressive treatment with steroids
and azathioprine or cyclosporin.
Morphoea
Morphoea is localized scleroderma.
CLINICAL FEATURES
One or more thickened, variably sized sclerotic plaques develop over the trunk or
limbs. A mauve colour at rst, they become brownish later (Fig. 6.16). It is mostly
a disease of young adults, but involvement of the face and scalp in children produces an en coup de sabre deformity. Morphoea generally gradually remits after
a period of 23 years. Histologically, there is marked replacement of the subcutaneous fat with new collagen, which has a pale, homogenized appearance. There is
no effective treatment.
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Dermatomyositis
VARIANTS
Generalized morphoea
This is a rare type of scleroderma that is conned to the skin but develops over
wide expanses of it, causing considerable limitation of movement and even
impeding breathing.
Lichen sclerosus et atrophicus
Dermatomyositis
Both muscle and skin are affected in this disabling disorder. Polymyositis is the
identical disorder without skin involvement.
CLINICAL FEATURES
Dull red to mauve areas develop over the face, backs of the hands, elbows, knees
and elsewhere. A particularly characteristic sign is the presence of a mauvish erythema on the upper lids and around the eyes, likened to the colour of the
heliotrope ower (Fig. 6.17). On the backs of the hands, the erythema affects the
paronychial folds and the skin over the metacarpals (Fig. 6.18).
Sometimes small areas of necrosis appear, due to an accompanying vasculitis.
Calcium is deposited in long-standing skin lesions.
There is proximal myositis, which causes pain and tenderness as well as profound weakness. If progressive, pharyngeal and respiratory muscles are affected
and the condition becomes life threatening. However, the disease generally remits
spontaneously.
LABORATORY FINDINGS
Muscle enzymes such as phosphocreatine kinase, aldolase and lactic dehydrogenase
are increased in the blood. Urine creatine is also a good indicator of disease activity. Muscle damage can also be assessed by muscle biopsy and electromyography.
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TREATMENT
Oral steroids are the mainstay of treatment and are given in sufcient dosage to
prevent further progress of the disease. Azathioprine and other immunosuppressive drugs are sometimes prescribed.
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Joint pain with some swelling is quite commonly noted. Cramping abdominal
pain and malaena occasionally develop as a result of submucosal haemorrhagic
oedema. Acute glomerulonephritis causes microscopic haematuria when renal
involvement is mild, but oliguria and renal failure in a very few severely affected
patients. The disorder remits spontaneously in most patients, but may recur
in some.
Pathology and pathogenesis
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Treatment
POLYARTERITIS NODOSA
Polyarteritis nodosa is a serious, rare inammatory disorder of large and
medium-sized arteries. Inammation of the vessel wall, which dilates aneurysmally,
causes rupture and ischaemic changes. Central nervous system, cardiovascular,
gastrointestinal and renal problems may all arise in this potentially fatal disease.
In the skin, a livedo reticularis pattern and persistent ulcers are seen.
NODULAR VASCULITIS
This is an uncommon inammatory disorder of the cutaneous vasculature of the
legs, seen predominantly in women.
Painful red and purpuric papules and nodules develop on the calves and elsewhere on the legs in recurrent crops over many years. Some may ulcerate, but
generally they disappear without sequel.
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Blistering diseases
CAPILLARITIS
There is a group of benign, persistent, mildly inammatory skin disorders in
which the focus of the abnormality appears to be in the papillary dermis and the
immediately subepidermal capillary vasculature. The term persistent pigmented
purpuric eruption seems appropriate, as they are persistent and because of
the damage to capillaries, causing leakage of blood and pigmentation from
haemosiderin staining. The lesions mostly occur on the lower legs and vary from
a macular, spattered appearance (Schambergs disease: Fig. 6.22) to an itchy, papular eruption (lichenoid purpuric eruption) or a macular golden eruption (lichen
aureus: Fig. 6.23). These disorders generally cause little disability and remit spontaneously after a variable period.
Blistering diseases
Many inammatory skin disorders can produce blistering at some stage in their
natural history. In the primary blistering diseases, blistering is the major feature
of the disease and a direct result of the initial pathological process. The different
blistering diseases are given in Table 6.5.
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Cicatricial pemphigoid
Erythema multiforme
Dermatitis herpetiformis
Epidermolysis bullosa
Intraepidermal
Pemphigus
vulgaris
vegetans
erythematosus
foliaceous
Treatment
Patients with widespread blistering may need to be nursed in hospital and treated
as though they had severe burns. High doses of corticosteroids (60 mg per day of
prednisone, or even more) are needed to control the disease. Immunosuppressive
treatment with azathioprine or methotrexate is usually started simultaneously. The
blisters themselves should be treated with wet dressings.
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Dermatitis herpetiformis
In the latter disorder, and in some blistering conditions in adults, IgA is deposited instead of IgG.
Dermatitis herpetiformis
Intensely itchy vesicles, papulovesicles and urticarial papules appear in crops over
the knees, elbows, scalp, buttocks and around the axillae (Fig. 6.27). Most patients
with dermatitis herpetiformis (DH) have a mild gastrointestinal absorptive defect
due to gluten enteropathy, as in patients with coeliac disease. Some diseases with
an immunopathogenetic component are more common in patients with DH,
including thyrotoxicosis, rheumatoid arthritis, myasthenia gravis and ulcerative
colitis. The disorder is persistent but uctuates in intensity.
LABORATORY FINDINGS
Small-bowel mucosal biopsy reveals partial villous atrophy in 7080 per cent of
patients with DH. Minor abnormalities of small-bowel absorptive function are
Figure 6.27
Vesiculopapules in
dermatitis herpetiformis.
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also common. Biopsy of new lesions demonstrates that the vesicle forms subepidermally and develops from collections of inammatory cells in the papillary tips
(the papillary tip abscess: Fig. 6.28). Direct immunouorescent examination
reveals the presence of IgA in the papillary tips in the skin around the lesions in
all patients.
TREATMENT
The skin lesions can be suppressed with the drug dapsone (50200 mg per day)
in most patients. Unfortunately, however, dapsone has many toxic side effects,
including haemolysis, methaemoglobinaemia, sulphaemoglobinaemia and rashes
such as xed drug eruption. A gluten-free diet will improve the gastrointestinal
lesion and improves the skin disorder in many patients after some months.
Epidermolysis bullosa
This is not a single disorder, but a group of similar, inherited blistering diseases.
The blistering is caused by various congenital structural and metabolic defects.
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Pemphigus
soles of the feet and not prove troublesome until adolescence. As with most genodermatoses, these conditions persist throughout life. There is no effective treatment other than to avoid trauma and to keep the blistered areas clean and dry.
Pemphigus
Pemphigus causes blistering because of a loosening of desmosomal links between
epidermal cells caused by immunological attack. There are several types. They are
all rare, but pemphigus vulgaris (PV) is the least rare. In PV, the split occurs within
the epidermis just above the basal layer (suprabasal). The lesions are thin-walled,
delicate blisters that usually rapidly rupture and erode (Fig. 6.29). They occur anywhere on the skin surface and very frequently occur within the mouth and throat,
where they cause much discomfort and disability. The disorder is persistent,
although uctuating in intensity. Before adequate treatment became available, it
was usually fatal.
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LABORATORY FINDINGS
In more than 90 per cent of patients, there is a detectable circulating antibody
directed to the area between epidermal cells. The titre of the antibody reects the
severity of the disease. The presence of the antibody and its titre are determined
by indirect immunouorescence methods. Biopsy reveals the intraepidermal split,
with rounded up epidermal cells (known as acantholysis). Direct immunouorescence examination of the perilesional involved skin will show the presence of antibody of the IgG class and the complement component C3 between epidermal cells.
TREATMENT
The patients should be treated as though they had burns and, if severely affected,
need in-patient care. Large doses of systemic steroids are required to control the
blistering (doses of up to 100 mg prednisone are sometimes given). Immunosuppressive therapy with azathioprine or methotrexate should be started simultaneously. Treatment with cyclosporin and with gold, as for rheumatoid arthritis,
has also been used.
VARIANTS
Pemphigus vegetans
This is a rare form of pemphigus in which the intraepidermal split is high within
the epidermis. It can cause erosions and scaling rather than blistering and can be
mistaken for sebborrhoeic dermatitis.
Pemphigus erythematodes
Drug eruptions
Most drugs have side effects as well as pharmacological effects, and skin disorders
are a frequent form of drug side effect. These can mimic many of the spontaneously occurring skin disorders as well as producing quite specic changes.
Drug-induced skin disorder can develop after the initial dose or after a short
period of time during which sensitization has taken place. Other problems, such
as pigmentations or hair anomalies, may take some months to appear. Often, a
rash occurs after taking the drug for some time, without apparent reason.
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Drug eruptions
It is important that drug reactions are suspected when the nature and cause
of a skin disorder are in doubt, as drugs in one shape or form are taken by a
substantial proportion of the population. Drug eruptions do not only stem from
orthodox prescribed drugs, but are also caused by cough medicines, analgesics,
laxatives or other over-the-counter symptomatic remedies, and enquiry must
also be made about these possibilities.
The diagnosis of a drug eruption is difcult to conrm, as there are few laboratory tests available. Currently, the only useful specic laboratory tests are those
dependent on there being specic IgE directed to the particular drug penicillin
is the only drug of importance that can be detected in this way (radio allergoabsorbent test, RAST).
Skin biopsy may assist in eliminating other causes of an eruption. The most
useful diagnostic test is the challenge, in which the suspected agent is administered to determine whether the condition recurs or is aggravated. Clearly, this is
not possible in the case of potentially severe or life-threatening conditions. Even
when this is not the case, it should only be performed with the patients consent
and if important information may be obtained that is relevant to the care of the
patient. The smallest possible dose should be given and the patient should be carefully observed subsequently.
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Exanthematic eruptions
PHOTOSENSITIVITY RASHES
In this group of drug-induced conditions, the rash is conned to the lightexposed areas and is wavelength dependent, i.e. it only reacts to particular wavelengths in the solar ultraviolet spectrum. The rash itself is red and papular or
plaque-like (Fig. 6.30). Some drugs seem able to provoke a phototoxic eruption,
which is seen in many patients to whom the drug is given and is dose dependent,
and others cause a photoallergic rash in which a photoallergen has formed and
which only affects a few individuals. Tetracyclines and sulphonamides may cause
a phototoxic response. The phenothiazines may cause either a phototoxic or a
photoallergic reaction.
Blistering rashes
Naproxen and frusemide may cause a pseudoporphyria-like rash in the lightexposed sites. Nalidixic acid may also cause blistering. Captopril and penicillamine may cause a pemphigus or a pemphigoid-like eruption.
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Summary
This not uncommon drug reaction causes inammatory patches to appear within
hours at the same sites on every occasion the drug is administered. The areas
become inamed, and may even blister before subsiding when the drug is
stopped, leaving pigmentation (Fig. 6.31). Numerous drugs, including dapsone,
the sulphonamides, tetracycline and mefenamic acid may be responsible.
Lupus erythematosus-like rashes
TREATMENT
Treatment of all drug eruptions consists of identifying the causative drug and
then stopping it. Care must be taken to see that the offending agent or one with
cross-reacting chemical groups is not given again.
Summary
Urticaria and angioedema result from histamine
release from mast cells and are characterized by
transient, itchy weals or deeper swellings.
Dermographic weals are elicited by rm stroking
with a blunt object.
The cause of chronic urticaria remains
undiscovered in most patients, but in a few food
hypersensitivities, drug sensitivity and physical
stimuli are found to be responsible. In a
substantial minority, an antibody to mast cells
has been found, so that the disorder can
be thought of as autoimmune. In cholinergic
urticaria, small, itchy weals occur after exercise
or hot baths.
Antihistamines of the H1 type are the most
effective in suppressing urticaria.
Erythema multiforme is caused by infections such
as herpes simplex and orf, as well as by drugs and
systemic diseases. It is an acute exanthematic
disorder, characterized by maculopapular lesions,
some of which are annular and may blister. The
mucosae are often affected.
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C H A P T E R
Infections
98
Skin cancers
99
99
Psoriasis
100
100
Drug-induced immunodeciency
100
101
Congenital immunodeciencies
101
102
Summary
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Infections
When the disease is activated, the patient becomes subject to opportunist infections as well as to an increased incidence and severity of usually mild and commonplace infections.
FUNGUS INFECTIONS
Dermatophyte infections, including nail infection, are extensive and difcult to
clear. Candidiasis is often a major problem, especially in the mouth and oropharynx. Systemic spread of Candida infection is unfortunately not uncommon and
often a terminal event. Pityrosporum ovale causes extensive eruptions of pityriasis
versicolor. It may also be responsible for a troublesome and persistent truncal folliculitis in some patients (Fig. 7.1) and for the common problem of severe seborrhoeic dermatitis seen in others. Various deep fungus infections are common,
particularly in hot and humid parts of the world.
VIRAL INFECTIONS
Viral warts may become very extensive and troublesome. Mollusca contagiosa
lesions may be both larger than usual and present in very large numbers (Fig. 7.2).
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Herpes simplex infection may be a particular problem, with extensive and persistent skin involvement resulting in scarring. Herpes zoster is similarly a troublesome infection in AIDS and may be the initial manifestation. It may look unlike
ordinary herpes zoster and may cause considerable pain and tissue destruction
as well as spreading outside the dermatomes in which it began.
BACTERIAL INFECTIONS
Tuberculosis and syphilis are both major problems for individuals with AIDS.
Both disorders progress rapidly and are responsible for extensive and severe disease in AIDS patients. Infections with mycobacterial species that do not generally
infect humans may also be seen. Epithelioid angiomatosis is due to infection with
a bacterial micro-organism similar to the bacillus causing cat scratch disease. It
causes Kaposis sarcoma-like lesions (see below) and a widespread eruption of red
papules.
Skin cancers
Depressed delayed hypersensitivity also results in failure of immune surveillance
and the development and rapid progression of many forms of skin cancer. Viral
infection may also be at work in the development of the disorder known as
Kaposis sarcoma, which mainly accompanies AIDS contracted from homosexual
contact. Mauve, red, purple or brown macules, nodules or plaques may ulcerate
and may spread to involve the viscera. Kaposis sarcoma is a frequent cause of
death in patients with AIDS.
Case 6
Simons dandruff gradually worsened and he developed seborrhoeic dermatitis of
the skin around his ears and nose. At the age of 23, he was surprised that he
was also developing numerous viral warts and mollusca contagiosa. His partner,
Peter, thought that they should both have tests for HIV disease and both men
were found to be positive.
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SCABIES
Scabies seems to spread very quickly and to cause extensive and severe involvement
in patients with AIDS. It also causes severe itching.
SEBORRHOEIC DERMATITIS
Another cause of itching in AIDS is seborrhoeic dermatitis. This is common
and extensive in patients with AIDS, presumably due to massive overgrowth of
Pityrosporum ovale and whatever other micro-organisms are involved (Fig. 7.3).
Psoriasis
Drug-induced immunodeciency
Patients who have organ transplants of kidneys, heart or liver are maintained on
corticosteroids and azathioprine, cyclosporin or tacrolimus for the rest of their
lives. Patients with autoimmune disorders such as systemic lupus erythematosus,
rheumatoid arthritis or chronic renal disease, and those with psoriasis and some
eczematous diseases, are also treated with immunosuppressive drugs for varying
lengths of time. The cutaneous side effects from the immunosuppression are not
usually as prominent as in AIDS patients, but depend on the extent and length of
the immunosuppression.
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Congenital immunodeciencies
Patients with renal allografts have most problems, maybe because they are treated
continuously for longer periods than most of the other groups. They are prone to
the development of numerous warty lesions on the hands and face after about
8 years of immunosuppression some 25 per cent were found to have warty lesions
in one British study (Fig. 7.4). These are either viral warts or solar keratoses, or
lesions which are somewhere in between! It may be that many of the viral warts
directly transform into pre-neoplastic lesions.
It should be noted that photochemotherapy with ultraviolet radiation of the
A type (PUVA) treatment (see page 141) also causes depression in delayed hypersensitivity and this is probably relevant to the development of skin cancer in
patients with psoriasis treated with PUVA some years previously.
Congenital immunodeciencies
Infantile agammaglobulinaemia is inherited as an X-linked recessive disorder.
There are no plasma cells in the marrow and the patients are susceptible to severe
pyoderma and numerous warts. In severe combined immunodeciency, there is
depression of circulating lymphocytes and levels of all immunoglobulins. Patients
are susceptible to all infections and usually die between the ages of 1 and 2 years. It
is inherited as either a sex-linked recessive or an autosomal recessive characteristic.
Ataxia telangiectasia (autosomal recessive) is characterized by cerebellar degeneration, telangiectasia on exposed skin developing progressively, lymphopenia and
depressed levels of IgA.
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REITERS SYNDROME
This disorder occurs as a sequel to non-specic urethritis in men and, less commonly, to bowel infection, and probably results from infection with a Mycoplasma
organism. There is usually an accompanying arthritis and spondylitis and occasionally a conjunctivitis. Psoriasiform skin lesions develop on the soles and toes. These
are often severe, persistent, aggressive and pustular (keratoderma blenorrhagica).
Inamed, red, scaling patches may also develop on the glans penis (circinate balanitis). There is a curious preponderance of patients with the HLA B27 haplotype.
GONORRHOEA
This venereal disease, which predominantly affects urethral epithelium, is caused
by the delicate intracellular Gram-positive diplococcus the gonococcus. The
skin is only affected during gonococcaemia, when small purpuric and pustular
vasculitic lesions suddenly appear in the course of a pyrexal illness (Fig. 7.5).
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SYPHILIS
Syphilis has once again become of major importance with the emergence of AIDS.
This is both because the syphilitic chancre serves as a portal of entry for the HIV
virus and because the manifestations of syphilis are much more dramatic in AIDS
patients.
The disease is caused by the delicate spirochaetal micro-organism Treponema
pallidum, which is transmitted by contact between mucosal surfaces.
Clinical features
Characteristically, the incubation period is 990 days and the rst sign is the
appearance of the chancre at the site of inoculation, usually on the glans penis,
prepuce or, less often, on the shaft in men and on the vulva in women. In homosexuals the chancre appears around or in the anus. The chancre is of variable size
(0.53 cm in diameter) and has a sloughy and markedly indurated base. Untreated,
it heals after 38 weeks.
This primary stage of the disease is followed by a brief quiescent phase of from
2 months to up to 3 years before the secondary stage occurs. In secondary syphilis
there are signs of systemic upset with mild fever, headache, mild arthralgia, generalized lymphadenopathy and skin manifestations, including an early widespread
macular rash, involving the palms (Fig. 7.6), and a later papular or lichenoid eruption. Thickened, warty areas (condylomalata) appear perianally and in other moist
exural sites (Fig. 7.7). Ulcers appear on the oral mucosa (snail-trail ulcers).
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After resolution of the secondary stage, there is a latent period without signs or
symptoms, lasting for 550 years. The tertiary stage takes protean forms and
includes cardiovascular disease with aneurysm formation, central nervous disorder, either as tabes dorsalis or general paralysis of the insane, and ulcerative or
gummatous lesions that may occur on the skin or on mucosal surfaces.
Diagnosis
TREATMENT
The treatment of syphilis is by parenteral penicillin over a 10-day period. One intramuscular injection of procaine penicillin 600 000 IU daily for 10 consecutive days is
adequate. A proportion of patients develop a fever and possibly a rash after starting
treatment (JarischHerxheimer reaction). More serious reactions can also occur.
Summary
AIDS is caused by a retrovirus the Human Immunodeciency Virus (HIV), which is transmitted by
sexual contact. It is characterized by depressed
delayed hypersensitivity and susceptibility to many
skin infections, including candidiasis, pityriasis
versicolor, molluscum contagiosum, warts, herpes
simplex, herpes zoster as well as tuberculosis and
syphilis. Seborrhoeic dermatitis, pruritic folliculitis
and Kaposis sarcoma are other skin disorders
occurring in AIDS. Steroids and immunosuppressive
drugs result in immunosuppression, and depressed
delayed hypersensitivity is also seen in Hodgkins
disease, vitamin A deciency and after UVR
exposure. In some cases, immunodeciency is
inherited.
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C H A P T E R
Eczema
(dermatitis)
Atopic dermatitis
105
Seborrhoeic dermatitis
114
117
118
119
Contact dermatitis
121
125
Summary
126
The term eczema includes several disorders (see Table 8.1) in which inammation
is focused on the epidermis. Typically, epidermal cells accumulate oedema uid
between them (spongiosis: Fig. 8.1), leading to vesicles in the most severe and
acute cases. Inammatory cells and vasodilatation accompany the oedema that is
also present in the dermis of the affected area.
Some types of eczema stem from uncharacterized constitutional factors
(endogenous or constitutional eczema), whereas others are the result of an external injury of some sort. The clinical picture varies according to the provocation,
the acuity of the process and the site of the involvement.
Atopic dermatitis
DEFINITION
This is a very common, extremely itchy disorder of unknown cause that characteristically, but not invariably, affects the face and exures of infants, children,
adolescents and young adults.
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Eczema (dermatitis)
Synonyms
Frequency/age group
Remarks
Atopic dermatitis
Neurodermatitis
Besniers prurigo
Infantile eczema
Seborrhoeic
dermatitis
Infectious eczematoid
dermatitis
Discoid eczema
Nummular eczema
Uncommon, mainly in
middle-aged individuals
Cause unknown
Lichen simplex
chronicus
Circumscribed
neurodermatitis
Eczema craquele
Asteatotic eczema
Uncommon, restricted
to the elderly
Venous eczema
Stasis dermatitis
Gravitational eczema
Delayed hypersensitivity
response to a specic agent
Not uncommon,
mainly in adults
Allergic contact
dermatitis
Primary irritant
contact dermatitis
Photosensitivity
eczema
Occupational dermatitis
Housewives eczema
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Atopic dermatitis
(a)
(b)
Figure 8.3 (a) Excoriations of the wrists in atopic dermatitis. (b) Excoriated, thickened eczematous area over the
sacrum.
CLINICAL FEATURES
Signs and symptoms
The major issue as far as this disease is concerned is itching. The patient is constantly
itchy and restless, but subject to irregular episodes of intense and quite disabling
intensication of the pruritus. The itchiness is made worse by changes in temperature, by rough clothing (such as woollens) and by sundry other minor environmental alterations. This symptom greatly disturbs sleep and the whole family
becomes affected. Scratching results from the severe pruritus in all except infants
under the age of 2 months. Patients also rub the affected itching parts they
frequently rub their eyes with the index nger knuckles (Fig. 8.2). The incessant
scratching and rubbing result in simple, linear scratch marks (excoriations:
Fig. 8.3) and chronic thickening of the skin characterized by accentuation of the
skin markings known as lichenication (Fig. 8.4). This is due to massive epidermal hypertrophy as well as oedema and inammatory cell inltrate in the
upper dermis (Fig. 8.5).
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Eczema (dermatitis)
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Atopic dermatitis
The cheeks are often pale and this feature, taken together with crease lines just
below the eyes (known as Denny Morgan folds) due to continual rubbing, makes
the facial appearance quite characteristic (Fig. 8.9). Running a blunt instrument
(such as a key) over affected skin produces a white line in about 70 per cent of
patients (Fig. 8.10) known as white dermatographism. This is the reverse of the
normal triple response and disappears when the condition improves. This unexplained paradoxical blanching is similar to that seen after intracutaneous injection of methacholine or carbamyl choline in atopic dermatitis patients.
CLINICAL VARIANTS
In patients with black skin, there are often numerous follicular papules in
affected areas (Fig. 8.11). In lichenied areas in black-skinned patients, there
may be irregular pigmentation, with hyperpigmentation at some sites and loss
of pigment at others.
Some individuals lose their childhood eczema only to develop chronic palmar
eczema in later years. This is believed also to be a manifestation of atopic disease.
ASSOCIATED DISORDERS
Patients with atopic dermatitis quite often also suffer from asthma. Some 30 per
cent will also have had asthma before their skin disorder has healed. There is no
particular synchronization, and worsening or remission of one has no particular
implication for the other. Hay fever is also more common in atopic dermatitis
patients, but the activity and severity have no link to the skin disorder.
Atopic dermatitis, asthma and hay fever seem to share pathogenetic mechanisms
in which aberrant immune processes play an important part. These three atopic
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Eczema (dermatitis)
disorders cluster in families and the tendency to one or the other or all is inherited
in an as yet uncharacterized way. Chronic urticaria (see page 71) and alopecia areata
(see page 271) occur more often in atopic dermatitis patients. The skin of patients
with atopic dermatitis is more vulnerable to both chemical and mechanical trauma
and has an unfortunate tendency to develop irritant dermatitis.
COMPLICATIONS
Patients with atopic dermatitis are frequently troubled by skin infections. Pustules
and impetiginized areas represent pyococcal infection and are the most common
expression of this propensity. They are easily treated, but tend to recur. Cellulitis
may also develop, giving rise to fever and systemic upset. Viral warts and mollusca
contagiosa are also more frequent and more extensive than in non-eczematous
subjects.
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Atopic dermatitis
Herpes simplex sometimes causes a severe and extensive rash in atopic dermatitis patients, who may develop fever and severe systemic upset, but recover after
1014 days.
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Eczema (dermatitis)
MANAGEMENT
Several points need to be kept rmly in mind.
Topical corticosteroids
Topical corticosteroids are the most useful topical agents for the treatment of atopic
dermatitis (see page 307). However, these drugs are only suppressive and need to be
given over long periods. Toxic side effects, such as skin atrophy, pituitaryadrenal axis
suppression and masked infection, are ever-present possibilities. Sudden withdrawal
of treatment can lead to a sudden and severe rebound aggravation of the eczema
and it is prudent to use the least potent corticosteroid preparation that is effective.
Topical corticosteroids may become less effective with continued use, but changing
to another preparation of similar potency will regain control. This phenomenon of
acquired tolerance is known as tachyphylaxis and is as yet unexplained.
There are many corticosteroids and less potent agents, such as hydrocortisone,
clobetasone 17-butyrate, urandrenolone and desoxymethasone, that are particularly suitable for infants with active eczema.
Creams, lotions and gels are less helpful vehicles for the corticosteroids and are
less useful than greasy ointments. Application once or twice daily is quite adequate.
Recently, a topical immunosuppressive agent tacrolimus (Protopic) has
become available. This agent is quite effective and does not have the skin-thinning
or pituitaryadrenal axis suppressive activity of corticosteroids.
Emollients
Emollients have hydrating effects on the skin in eczema because of their occlusive
properties. They reduce scaling and improve skin texture and appearance. They
improve the extensibility of skin and reduce ssuring as well as decreasing the
pruritus and inammation via unknown mechanisms.
All emollients seem to have much the same degree of effect providing they
are sufciently greasy and occlude the skin surface. The most important issues are
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Atopic dermatitis
how frequently they are applied and whether the patient actually uses them! They
should be applied at least three times daily for the best effect and more frequently
if possible their effects only last 2 hours or so. A bath oil or an emollient skin
cleanser (e.g. emulsifying ointment BP) may also help.
Tar preparations
Coal tars are used for eczema and psoriasis. The generic preparations (e.g. tar ointment or tar and salicylic acid ointment BP) are not popular because of the smell and
messiness associated with their use, but modern proprietary preparations are more
acceptable (e.g. Clinitar cream). Their anti-inammatory action is little understood and they are best employed for chronic lichenied areas of eczema. They can
irritate the skin and have caused concern because of a potential for carcinogenicity.
Systemic agents
Some patients with severe disease do not respond to topical measures. For this
group there are several options. These include photochemotherapy with one or
another of ultraviolet radiation (see page 141), systemic steroids and cyclosporin.
Some patients improve after sun exposure, and phototherapy of some type
may be of assistance for them. This may help 5075 per cent of severely affected
patients, but has to be balanced against the long-term hazards of skin cancer (see
page 207 et seq.). Systemic steroids suppress the eczema, but the cost in severe longterm toxicity, including osteoporosis, skin fragility, susceptibility to infection and
pituitaryadrenal axis suppression, probably outweighs the short-term benets.
Cyclosporin is a fungal metabolite peptide with immunosuppressive effects
that is found to be helpful for some patients with severe psoriasis (see page 140).
It has been found to have a dramatic effect in patients with severe, generalized
atopic dermatitis at a dose of 35 mg/kg body weight per day. As with most effective drugs, there are toxic side effects, which, in the case of cyclosporin, include
nephrotoxicity and hypertension. None of these systemic drugs or photochemotherapy with UVA (PUVA) should be given without consultation with a specialist
with experience in the benets and side effects of the various treatments.
Unfortunately, cyclosporin does not work when employed topically.
Antimicrobial agents
Patients with atopic dermatitis are particularly prone to skin infection. Infection
with staphylococci and possibly other bacteria cause pustules, impetiginized lesions
and cellulitis and may also be responsible for are-ups of the dermatitis. This is
the reason why appropriate antibacterial measures by themselves seem to be
benecial. Bacterial swabs should be taken before starting treatment with either
topical or systemic antibacterial agents. Antimicrobial bath additives such as a povidone iodine or a hexachlorophane preparation may assist. The infected area can be
soaked or bathed in 1 in 8000 potassium permanganate solution or aluminium
subacetate solution. Topical neomycin or mupirocin may be used, but other antibiotics should be avoided because of the problem of resistance. If there is evidence
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Eczema (dermatitis)
of signicant infection in several sites that may be aggravating the atopic state,
systemic antibiotics should be given, taking into account local and current policy
with regard to penicillin resistance.
Seborrhoeic dermatitis
DEFINITION
This is a common eczematous disorder that characteristically occurs in hairy
areas, on the exures and on the central parts of the trunk, and is now believed
to be at least in part due to overgrowth of the normal skin ora in the regions
affected.
CLINICAL FEATURES
Signs and symptoms
Reddened, itchy patches appear at the affected sites, which may become either scaly
or exudative and crusted. Scaling is a common feature when the condition
develops insidiously. Often, mild scaling occurs without erythema, as it does, for
example, on the scalp as dandruff . When severe, the eyebrows may also be
affected. Other facial areas may become involved such as the nasolabial folds, the
paranasal sites, the external ears and the retroauricular folds (Figs 8.12 and 8.13).
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Seborrhoeic dermatitis
(a)
(b)
Figure 8.14 (a) Exudative lesions of seborrhoeic dermatitis in the groin area. (b) Seborrhoeic dermatitis of intertriginous
areas in the groin of an obese woman.
Scaling and erythema of the eyelid margins (marginal blepharitis) may also occur.
Another type of lesions seen in seborrhoeic dermatitis is a form of folliculitis. This
seborrhoeic folliculitis is marked by numerous small papules and papulopustules
originating in the hair follicles. The usually commensal yeast-like micro-organism
Pityrosporum ovale seems to have taken on an aggressive role, causing the inammatory lesions seen.
DIFFERENTIAL DIAGNOSIS
In the groin area, it is important to distinguish exural psoriasis (see page 129)
and ringworm infection (tinea cruris; Table 8.2). Ringworm rashes are usually
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Eczema (dermatitis)
Tests
Ringworm
Microscopy and
culture of scales
Seborrhoeic
dermatitis/
intertrigo
None available
Clothing
dermatitis
Patch testing
asymmetrical and do not reach up right into the groin apices. There is usually a
raised advancing edge to ringworm and a tendency to clear centrally. Mycological
testing is so simple and useful and the results of misdiagnosis so embarrassing
that all should become procient at skin scraping and recognition of fungal
mycelium (see page 38).
TREATMENT
The major aims in the treatment of seborrhoeic dermatitis are the removal of the
precipitating microbial cause and the suppression of the eczematous response.
For this purpose, topical preparations containing both 1 per cent hydrocortisone
and an imidazole such as miconazole or clotrimazole may be all that is required
for patients with limited disease. A preparation containing lithium succinate has
also been useful. Sulphur and salicylic acid preparations are antimicrobial and
keratolytic and, although inelegant, appear quite effective when all else fails!
Exudative intertriginous areas in the major body folds rapidly respond to bed
rest to avoid further friction between opposing skin surfaces and bland lotions
or weak, non-irritating antibacterial solutions for bathing and wet dressings.
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CLINICAL FEATURES
Signs and symptoms
Slightly raised, pink-red, scaly discs, varying in diameter from 1 cm to 4 cm, appear
on the arms and legs and, less frequently, on the trunk (Fig. 8.16). The disorder is
usually quite itchy and the skin on the arms and legs is often dry as well.
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Eczema (dermatitis)
Features
Psoriasis
Discoid eczema
Ringworm
Bowens disease
DIFFERENTIAL DIAGNOSIS
The condition has to be distinguished from psoriasis, in which the margins are
more distinct; from ringworm, which usually spreads peripherally and has a raised
margin; and from Bowens disease, which is mostly restricted to the light-exposed
areas and is usually one or two solitary red, scaling patches (Table 8.3).
TREATMENT
Weak and moderately strong corticosteroid preparations (e.g. 1 per cent hydrocortisone, clobetasone or desoximethasone are all suitable) applied once or twice
daily usually suppress the disorder. Emollients and emollient cleansers are also
helpful as adjuncts.
CLINICAL FEATURES
Signs and symptoms
The most common affected sites are the shins, the fronts and sides of the thighs,
extensor aspects of the upper arms and forearms, and the back. Involved skin
is pink, roughened and supercially ssured, giving a crazed appearance (Fig.
8.17). The areas affected are more sore than itchy. The condition has a very
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TREATMENT
The condition responds to emollients and, if necessary, 1 per cent hydrocortisone
ointment when the atmosphere is humidied and vigorous washing stops.
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Eczema (dermatitis)
CLINICAL FEATURES
Signs and symptoms
The medial aspect of the ankle, the back of the scalp, the extensor aspects of the
forearms, the wrists and the genitalia are predisposed to this disorder. The condition
is extremely itchy and patients complain bitterly about the intense local irritation.
The lesions are characteristically raised, irregular, red plaques with well-dened
margins, which have exaggerated skin markings (lichenication) over the scaling
surface (Fig. 8.18). If the itching is persistent and intense and the resultant scratching vigorous, the affected sites may become very thickened, raised and excoriated.
The resultant lesion is known as a prurigo nodule (Fig. 8.19). When many such nodules occur over the surface, the condition is known as prurigo nodularis.
The disorder is quite common in middle-aged subjects of either sex and all races.
It may be more common in the Indian subcontinent. It is a very stubborn and persistent disorder, which may stay unchanged for many years. Prurigo nodularis is
similarly stubborn and persistent.
DIFFERENTIAL DIAGNOSIS
Hypertrophic lichen planus (see page 145) may be difcult to distinguish, although
this disorder tends to be more mauve and be less regularly lichenied than lichen
simplex chronicus. Biopsy may be needed to distinguish these disorders with certainty. Lichen simplex chronicus may also resemble a patch of psoriasis.
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Contact dermatitis
The persistent scratching causes an increased rate of epidermal cell production and
accounts for the hypertrophy. The cause of the pruritus is unknown.
TREATMENT
The condition tends to persist regardless of the treatment prescribed. Highpotency topical corticosteroids, intralesional corticosteroids or preparations of
coal tar are sometimes helpful.
Case 7
The persistent itching of the thickened, scaling patches around the ankles and at
the back of the neck was extremely distressing for 68-year-old Michael. A biopsy
showed only thickening of the epidermis and some inammation, which was
diagnosed as lichen simplex chronicus. Michael had had the condition for at least
6 years and nothing seemed to help. One Tuesday morning he woke up with much
less itching and by the end of the week it was clear that the condition had gone
into remission for no known reason!
Contact dermatitis
Contact dermatitis may be caused by a direct toxic action of a substance on the
skin the so-called primary irritant dermatitis or by a substance inducing a
delayed hypersensitivity reaction allergic contact dermatitis. Both are common
and cause considerable loss of work and disability.
Primary irritant dermatitis is an eczematous rash that results from direct contact
with toxic irritating materials.
Clinical features
Scaly, red and ssured areas appear on the irritated skin (Figs 8.20 and 8.21). The
hands are most frequently affected. The palmar skin and the palmar surfaces of
the ngers are often affected, but the areas between the ngers and elsewhere on
the hands may also be involved. The condition may become exudative and very
inamed if the substances contacted are very toxic. This form of contact dermatitis causes considerable soreness and irritation. The ssures make movement very
difcult and effectively disable the victims.
Differential diagnosis
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Eczema (dermatitis)
An irritant substance will injure anyones skin if there is sufcient contact. However,
some individuals are more prone to develop primary irritant contact dermatitis
especially atopic subjects and those with fair skins who sunburn easily.
The disorder is seen particularly often in manual workers (occupational dermatitis) and housewives (housewives eczema). Builders, mechanics, hairdressers,
cooks and laundry workers are some of the groups that are frequently affected.
The condition causes considerable economic loss from loss of work. Contact with
alkalis, organic solvents, detergent substances, cement and particulate waste is
often responsible.
Prevention and management
Allergic contact dermatitis is an eczematous rash that develops after contact with
an agent to which delayed (cellular) hypersensitivity has developed.
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Contact dermatitis
Clinical features
The rash develops at the sites of skin contact with the allergen, but occasionally
spreads outside these limits for unknown reasons. The vigour and speed of the reaction vary enormously depending on the particular individual. When very acute, the
reaction develops within a few hours of contacting the responsible substance such
a speedy response is seen, for example, in the condition of poison ivy, which is
common in the USA. Itching is noticed at rst and then the area involved becomes
red, swollen and vesicular. Later, the area becomes scaled and ssured.
An enormous number of substances are capable of causing allergic contact
dermatitis. Nickel dermatitis is one of the commonest examples some 5 per cent
of women in the UK are said to be nickel sensitive. Affected individuals cannot
wear stainless-steel jewellery because of the nickel in the steel (Fig. 8.22) and
develop a rash beneath steel studs, clips and buckles. Patients who are nickel sensitive may also react to dichromate and other chromate salts.
Other examples include allergy to chemicals in rubber, for example mercaptobenzthiazole (MBT) and thiouram, and to formalin. These allergies may cause
dermatitis when wearing particular clothes, as, indeed, may sensitivities to dyes.
Allergies to lanolin (in sheep-wool fat and in many ointments and creams) and to
perfumes can cause dermatitis after the wearing of cosmetics. Lanolin, ethylene
diamine, vioform, neomycin and local anaesthetics may cause a dermatitis after
using a cream or an ointment. Dyes (such as the black hair dye paraphenylene
diamine) can also be the cause of allergic contact dermatitis (Fig. 8.23). Some
materials are notorious for causing sensitivity and are not often used topically
because of this, for example penicillin and sulphonamides.
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Eczema (dermatitis)
Allergic contact dermatitis is quite common, but not as common as primary irritant dermatitis. It is rare in children and uncommon in the elderly. It is seen in all
racial groups, although less so in black-skinned individuals.
Diagnosis of allergic contact hypersensitivity
Accurate history taking and careful examination identifying all involved areas are
very important. The denitive technique for diagnosing allergic contact hypersensitivity is patch testing. In this test, possible allergens are placed in occlusive
contact with the skin for 48-hour periods and the area is inspected 48 hours after
removal of the patch. A positive test is revealed by the development of an eczematous
patch with erythema, swelling and vesicles at the site of application. In practice,
low concentrations of allergen are applied to avoid false-positive primary irritant
reactions.
In most cases, a battery of the commonest allergens in appropriate concentrations is applied. Such a battery is shown in Table 8.4.
Table 8.4 Common antigens used in patch testing and
concentrations in which they are used
Antigen
Nickel sulphate
Balsam of Peru
Colophony
Chlorocresol
PPD base
MBT
Formalin
Potassium dichromate
Wool alcohols
Epoxy resin (Araldite)
Chloroxylenol
Neomycin
Cobalt chloride
Dowicil 200
Parabens
Thiuram-mix
Mercapto-mix
Perfume-mix
Kanthon CG
Primin
Ethylene diamine
Benzocaine
PPD paraphenylene diamine; MBT mercaptobenzthiazole.
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%
5
25
1
1
1
2
1
0.5
30
1
1
20
1
1
15
1
2
8
0.67
0.01
1
5
Antigen
pidermis
Dermis
T-lymphocyte
Peripheral
lymph
node
The sensitizing chemical (antigen) crosses the stratum corneum barrier and is
picked up by the Langerhans cells in the epidermis (Fig. 8.24). The antigen is then
processed by the Langerhans cell and passed on to T-lymphocytes in the peripheral lymph nodes. Here, some of the T-lymphocytes develop a specic memory
for the particular antigen and the population of these expands. This process of
sensitization takes some 1014 days in humans. After this period, when the particular antigen contacts the skin, the primed T-lymphocytes with the memory for
this chemical species rush to the contacted site and liberate cytokines and mediators that injure the epidermis and cause the eczematous reaction.
Treatment
It is vital to identify the sensitizing material and prevent further contact. The
eczema will subside rapidly in most cases after removal from the antigen. The use
of weak or moderately potent topical corticosteroids and emollients will speed
the resolution of the eczematous patches.
CLINICAL FEATURES
Itchy, pink, scaling areas develop on a background of the changes of chronic
venous hypertension (Fig. 8.25). The affected areas are often around venous ulcers,
but the margins of the eczematous process are poorly dened. Occasionally, the
process spreads to the contralateral leg and even to the thighs and arms.
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Eczema (dermatitis)
TREATMENT
Contact hypersensitivity must be identied and the patient advised to stop using
the agent responsible. The simplest of topical applications should be used white
soft parafn is suitable as an emollient and 1 per cent hydrocortisone ointment is
suitable as an anti-inammatory agent.
Summary
Eczema (synonymous with dermatitis) is
characterized by epidermal oedema (spongiosis)
and may be caused by external factors or result
from poorly understood endogenous or
constitutional factors. The former types of eczema
include allergic contact dermatitis and primary
irritant contact dermatitis, whereas amongst the
latter are atopic dermatitis, seborrhoeic dermatitis,
discoid eczema and lichen simplex chronicus.
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Summary
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C H A P T E R
Psoriasis and
lichen planus
Psoriasis
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142
Lichen planus
144
Summary
147
Psoriasis
Psoriasis is important because of its frequency, its recurrent nature and its tendency to disable a proportion of its victims.
DEFINITION
Psoriasis is a common, genetically determined, inammatory skin disorder of
unknown cause, which, in its most usual form, is characterized by welldemarcated, raised, red scaling patches that preferentially localize to the extensor
surfaces.
CLINICAL FEATURES
The lesions
Typical lesions are red, raised and scaly and have well-demarcated margins
(Fig. 9.1). Plaques vary enormously in size and shape. They often start out discoid,
but end up polycyclic (Fig. 9.2) as several lesions coalesce.
Sites affected
Psoriasis affects the extensor aspects of the trunk and limbs preferentially. The
knees, elbows and scalp are especially frequently affected (Fig. 9.3), although the
mucosae seem to be spared.
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Psoriasis
The nails are often affected and may show the so-called thimble pitting, separation of the nail plate from the nail bed (onycholysis), subungual debris, brownish-black discolourations and deformities of the nail plate (Fig. 9.4).
Flexural lesions, which occur in some patients, are most often seen in the major
body folds in the elderly, especially in those who are overweight. The groins and
genitalia, axillae, inframammary folds in women and the skin of abdominal folds
and the umbilicus in either sex are affected. The moistness of the exural areas
decreases the scaling and produces a moist and glazed appearance (Fig. 9.5).
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The face is not usually severely affected in psoriasis, although the scalp margin,
paranasal folds and retroauricular folds are quite often involved (Fig. 9.6).
Psoriasis sometimes appears at the site of a minor injury such as a scratch or
a graze (Fig. 9.7). This reaction, known as the isomorphic response or the Koebner
phenomenon, mostly occurs when the psoriasis is in active spreading phase. The
development of a skin disorder at the site of injury is characteristic of psoriasis,
but is also seen in lichen planus (see page 144) and discoid lupus erythematosus
(see page 79). Its cause is unknown.
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Psoriasis
disorder is less common in African and Asian groups, but detailed gures are not
available. It seems less of a problem in the Japanese and other Asian populations,
but may be becoming more frequent with the trend to Westernization.
The disease is more common in men than in women. There are two main peaks
of incidence, the rst of which is in the second half of the second decade of life.
Recently, it has been recognized that psoriasis may also occur for the rst time in
the seventh decade. In general, the younger the age of onset, the worse the outlook
as far as frequency, severity and persistence of the disease are concerned.
Psoriasis is a life-long disorder subject to unpredictable remissions and relapses.
Single episodes are uncommon and in the most frequent variety an episode in the
teenage years is followed by a series of attacks, each lasting weeks or months, in
the succeeding years.
GENETICS
Psoriasis is often familial, but does not appear to be inherited in any regular dominant, sex-linked or recessive way. With one parent affected, there is an approximately 30 per cent chance of a child being affected. With both parents suffering
from psoriasis, the chance that a child will develop the condition rises to 60 per
cent. In a recent survey in Sweden, it was found that 6.4 per cent of relatives of
families in which there was a patient with psoriasis were affected, compared to
1.94 per cent of controls. Non-identical twins have an approximately 20 per cent
chance of both being affected, and the concordance rate for identical twins seems
to be in the order of 70 per cent. Recent research indicated that, although no one
gene is responsible for the disease, the direct inheritance of susceptibility genes is
necessary for its development.
Psoriasis is associated with HLA groups HLA-B13, HLA-B17 and HLA-B37 as
well as with the class II antigen DR7. It is even more strongly associated with CW6
increasing the risk of the disease some 13 times in Caucasians.
DIFFERENTIAL DIAGNOSIS
Any red, scaling disorder can be mistaken for psoriasis, and vice versa (Table 9.1).
On the scalp, the most frequently seen disorder to be mistaken for psoriasis is seborrhoeic dermatitis (see page 114), although this usually affects the scalp diffusely
rather than in distinct plaques. Lichen simplex chronicus (see page 119) of the
scalp typically presents with a red, scaling patch on the occiput, which can look
very psoriasis-like. The intense itching and lichenied surface should serve to distinguish the two disorders.
Multiple patches of ringworm may appear very like psoriasis (Fig. 9.8), but the
lesions are often more ring-like than psoriasis and can be distinguished by microscopical examination of potassium hydroxide (KOH)-treated skin scrapings (see
page 38). Mycosis fungoides a T-cell lymphoma of skin often evolves through
a phase in which there are many red psoriasiform lesions on the trunk, but these
differ from psoriasis by being more irregular in shape and persistent.
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Discoid eczema
Bowens disease
Mycosis fungoides
Ringworm
On the legs, raised, round, red, scaling psoriasiform patches often turn out
to be Bowens disease in the elderly, or discoid eczema. Lichen simplex chronicus
around the ankles may also be difcult to distinguish.
Psoriasis of the palms (Fig. 9.9) is difcult to distinguish from eczema affecting these sites. Even after biopsy, the clinician may remain uncertain.
Supercial basal cell carcinoma lesions are sometimes several centimetres in
diameter and quite psoriasiform in appearance, but have a ne, raised, hair-like
margin.
CLINICAL VARIANTS
Guttate psoriasis
This disorder is mainly seen in children aged 714 years. Often, it develops some 24
weeks after an episode of tonsillitis or pharyngitis, mostly due to beta-haemolytic
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Psoriasis
Infantile napkin dermatitis (see page 229) sometimes takes on a very psoriasis-like
appearance and typical psoriatic lesions develop on the scalp and trunk. The true
relationship with psoriasis is unknown.
Erythrodermic psoriasis
Psoriasis sometimes progresses to generalized skin involvement. Typical plaquelike lesions disappear, the skin is universally red and scaly and the condition is
known as erythrodermic psoriasis. Patients who are seriously ill suffer from:
heat loss, and are in danger of hypothermia because of the increased blood
supply to the skin
water loss, leading to dehydration because of the disturbed barrier function of
the abnormal stratum corneum
a hyperdynamic circulation, because effectively there is a vascular shunt in the
skin; when the patients myocardium is already compromised because of other
factors, there is a danger of high output failure
loss of protein, electrolytes and metabolites via the shed scales and exudates;
patients may develop deciency states.
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Pustular psoriasis
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Psoriasis
Sometimes, the pustules become conuent so that lakes of pus develop just
beneath the skin surface. In other areas, there is a curious type of supercial peeling without pustules forming.
These patients are very unwell and require hospitalization. They can usually be
brought into remission by modern treatments (see below), but are subject to
recurrent attacks. The disorder sometimes affects infants and small children.
Other forms of pustular psoriasis
Occasionally, pustules may develop after strong topical or systemic corticosteroids
have been used and then abruptly withdrawn. Other rare variants of pustular psoriasis include:
acrodermatitis continua, in which there is a recalcitrant pustular erosive disorder on the ngers and toes around the nails and occasionally elsewhere
pustular bacterid, in which sterile pustules suddenly appear on the palms, soles
and distal parts of the limbs after an infection.
Arthropathic psoriasis
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joints are particularly affected. The disorder is more destructive than rheumatoid
disease. Bony erosion and destruction take place, leading to collapse of affected
digits (Fig. 9.14), justifying the term often used for this dreadful disease arthritis
mutilans.
Treatment may temporarily improve these joint complications of psoriasis, but
they tend to run a progressive course subject to remissions and relapses.
The epidermis shows marked exaggeration of the rete pattern and elongation
of the epidermal downgrowths with bulbous, club-like enlargement of their ends
(Fig. 9.15). The average thickness is increased from about three to four cells in the
normal skin to approximately 1215 cells in the psoriatic lesion. Many mitotic gures can be seen and the rate of epidermal cell production seems to be greatly
enhanced. The turnover time of psoriatic epidermis and stratum corneum is consequently very much shortened. Normally, it takes some 28 days for new cells to
ascend from the basal layer and travel through the epidermis and the stratum
corneum and reach the surface. In psoriasis, it takes some 4 days! Epidermal
nuclei are retained in the inefcient horny layer that results (parakeratosis).
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Psoriasis
The papillary capillaries are greatly dilated and tortuous to a degree not seen in
other inammatory skin disorders. Ultrastructurally it can be seen that there are
larger gaps than usual between the endothelial cells. These abnormal capillaries
are the last of the features to go during resolution.
AETIOLOGY
The cause of psoriasis is unknown, despite the enormous research effort that
has been made in the past three decades. Various hypotheses have been popular
at different times. One very obvious abnormality in psoriasis is the hyperplastic
epidermis with increased mitotic activity, and one line of intense investigation
was directed at the control of epidermal cell production in this disease. Attention
has moved away from this possibility in recent years and focused more on the
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TREATMENT
Patients with just a few plaques affecting the knees, elbows or elsewhere require
little treatment. In other patients, simple treatment with an emollient such as
white soft parafn, by itself or with 2 per cent salicylic acid, is sufcient when
used once or twice daily.
With more lesions and symptoms, more active topical treatment is needed.
Tar-containing preparations are less popular than previously, but may suit
some patients who can put up with the stinging, the unpleasant smell and the
staining. Tar has anti-inammatory and cytostatic activity and certainly has
mild anti-psoriatic effect. Proprietary tar preparations have some advantages
over the British National Formulary formulations. Tar shampoos for scalp
involvement are still popular.
Analogues of vitamin D3 are effective topical treatments; calcipotriol used once
or twice daily improves some 60 per cent patients after 6 weeks treatment. Used
alongside medium-potency corticosteroids, the efcacy is increased and the skin
imitation decreased. A preparation of calcipotriol formulated together with
betamethasone-17-valerate is now available as Dovobet, and does appear quite
effective. Tacalcitol is another vitamin D3 analogue, which, although effective
when employed topically, is not as potent as calcipotriol. Apart from skin irritation, there is the concern that sufcient of these D3 analogues will be absorbed to
cause hypercalcaemia. Fortunately, this has not proved to be a problem thus far.
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Psoriasis
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Retinoids are analogues of retinol (vitamin A) and have been found to exert
important actions on cell division and maturation. The orally administered
acitretin is of particular value in psoriasis. The drug benets patients with all
types of severe psoriasis after 34 weeks, but is of most help when used in combination with ultraviolet treatment. Its major drawback is that it is teratogenic and
can only be given to fertile women if they use contraception and are prepared to
continue using the contraceptive measures for 3 years after stopping treatment.
Other signicant toxicities include hyperlipidaemia and a possibility of hyperostosis and extraosseous calcication. In addition, it does have some hepatotoxicity
in a few patients (Table 9.2). These signicant toxicities are not common, but
minor mucosal side effects occur in all patients, including drying of the lips and
the buccal, nasal and conjunctival mucosae. Minor generalized pruritus and slight
hair loss also occur. Oral retinoids should only be prescribed by dermatologists,
i.e. those who are familiar with their effects.
Cyclosporin
Comment
Hyperlipidaemic effect
Hepatotoxicity
Bone toxicity
Minor
Drying and cracking of lips
In most patients
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Psoriasis
also dramatically effective in psoriasis when given in doses of 35 mg/kg per day.
Its toxic side effects include severe renal damage and hypertension. Its place in the
treatment of disabling and severe psoriasis is assured, but great care and constant
monitoring are required.
Treatment with ultraviolet radiation
Ultraviolet radiation (UVR) has long been known to have therapeutic effects in a
number of skin disorders, including psoriasis. A form of UVR treatment known
as PUVA is mainly used. PUVA is an acronym for photochemotherapy with ultraviolet radiation of the A (long-wave) type. The UVA is supplied by special uorescent lamps that emit at wavelengths of 300400 nm, housed in cabinets or
special frames over beds.
A photosensitizing psoralen drug is given orally 2 hours before exposure. The
main psoralen used is 8-methoxy psoralen, but 5-methoxy psoralen and trimethoxy
psoralen are sometimes used. The dose of 8-methoxy psoralen is 0.6 mg/kg. Alternatively, the patient bathes in water containing a psoralen and is then exposed to
UVR a few minutes later.
Ordinary sun lamps emitting UVB (290320 nm) can also be used to treat
psoriasis. The dangers of burning may be greater and the dangers of skin cancer
are similar to PUVA.
Both PUVA and UVB can be combined with topical dithranol, calcipotriol and
tazarotene or oral acitricin. These combinations reduce the danger of side effects
from UVR and reduce the likelihood of toxicity from the accompanying agent.
The dose of UVA is calculated (in Joules) from the output of the lamps and the
time of exposure. The dose required for clearance is approximately 50100 J/cm2
and care is taken to keep the dose as low as possible and certainly below a total
cumulated dose of 1500 J/cm2 to reduce the possibility of long-term side effects.
There are several long-term side effects (Table 9.3).
Increased incidence of squamous cell carcinoma of the skin (see page 207) up
to 10 or 12 times that in a control group of psoriatics after 10 years. Carcinoma
of the external genitalia in men is a particular problem. There is an increased
incidence of basal cell carcinoma and melanoma as well.
Increased solar elastotic degenerative change, with the appearance of ageing
and alteration of skin elasticity.
Cataracts can develop and all patients who receive PUVA must wear effective UVA protective goggles or sunglasses during exposure and for 24 hours
afterwards.
In the short term, nausea is often experienced and, if too long an exposure is
given, burning can occur. Patients who are sensitive to the sun or who coincidently have a disorder that can be aggravated by UVA exposure, such as lupus
erythematosus or porphyria cutanea tarda, should not be treated by PUVA.
So-called narrow-band UVR is UVR at a wavelength of 311 nm. It has recently
been introduced as an effective and less hazardous form of UVR treatment
(although there is uncertainty on this issue).
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Comment
Cataract
Photoageing
Burning
Other treatments
Numerous other treatments have been investigated in the past few years. These
range from propylthiouracil to fumaric acid derivatives and new immunosuppressive agents such as tacrolimus.
CLINICAL FEATURES
The commonest type of pityriasis rubra pilaris occurs in the late middle-aged or
elderly and is often of sudden onset. Usually, the disease begins on the face and
scalp, with pinkness and scaling, and spreads within a few days or a week or two
to involve the rest of the body. There is a characteristic orange hue to the redness,
and on the thickened palms there is a characteristic yellowish discoloration
(Fig. 9.18). Scattered amongst the red, scaling eruptions are islands of spared
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white skin (Fig. 9.19), and on the hands, thighs and sometimes elsewhere there
is a typical follicular accentuation due to the presence of hyperkeratotic spines
(Fig. 9.20).
There is also an infantile type which, although similar in many ways to the
adult form, tends to be much more stubborn and resistant to treatment.
The histological appearance is distinctive in that, although there is considerable
epidermal thickening, the accentuation of the dermal papillae and the undulations of the dermoepidermal junction are much less marked than in psoriasis.
TREATMENT
Many patients respond well to oral retinoids by mouth (see page 140) given in
the same manner as for psoriasis. Treatment by methotrexate has also been
advocated.
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Lichen planus
DEFINITION
Lichen planus is an inammatory disorder of skin of unknown origin but with a
prominent immunopathogenetic component. It is characterized by an eruption of
variable extent of typical mauve or pink, at-topped, itchy papules.
CLINICAL FEATURES
The typical lesion of lichen planus is a mauve or pink, at-topped, polygonal
papule, which often has a whitish lacework pattern on its surface (Wickhams
striae) (Fig. 9.21). The papules are often aggregated in some sites, for example the
front of the wrist (Fig. 9.22), but may also occur scattered sparsely over the skin
of the limbs and trunk. Usually, only a few lesions develop, but in some cases the
eruption may be dense and generalized.
The mucosae are often affected and lesions occur in the mouth in some 30
per cent of patients. A white lacework pattern on the buccal mucosa is the most
frequently observed type of lesion (Fig. 9.23), but the tongue and elsewhere in the
mouth may also be involved, with white lacework, whitish macule or punctuate
lesions. The male genitalia are also sometimes affected (Fig. 9.24). The nails
develop longitudinal ridges in 510 per cent of patients (Fig. 9.25). Less commonly, a destructive process develops in which the nail plate is lost and the nailforming tissue (the nail matrix) is damaged.
The scalp is sometimes affected and then localized patches of hair loss and
scalp scarring occur.
As lesions heal, they atten and often leave a pigmented patch, which persists
for some weeks.
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Lichen planus
The commonest variant is hypertrophic lichen planus, in which thickened, mauvish papules or nodules of irregular shape with a warty or scaling surface develop
(Fig. 9.26). Solitary hypertrophic lesions may appear in the course of ordinary
lichen planus or develop as solitary lesions.
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Annular lichen planus describes the situation in which lichen planus lesions
have fused to give a ring-type conguration. This odd variant sometimes occurs
on the male genitalia and lower abdomen, but rarely elsewhere.
Lichen nitidus is a rare variant of lichen planus in which numerous tiny, pink,
at-topped papules develop.
Bullous lichen planus is a very rare variant in which blistering occurs on some
lesions.
Lichen plano-pilaris predominantly involves the hair follicles. Affected sites lose
their terminal hair and develop horny spines, which project from the affected hair
follicles.
AETIOPATHOGENESIS
Lichen planus appears to be in the general category of autoimmune diseases and
patients affected by it have a higher frequency of other autoimmune disorders
than a comparable unaffected population. Myasthenia gravis and vitiligo seem
particularly associated.
The disease is not uncommon in Europe, possibly accounting for some 24
per cent of new patients in skin clinics, but is quite uncommon in the USA. It appears
to be a more frequent problem in parts of Asia. There does not seem to be a major
genetic component to the disease.
Most patients are free of lesions after a year. Hypertrophic lesions tend to last
for many years.
There are characteristic histopathological changes (Fig. 9.27).
(a)
(b)
Figure 9.27 (a) Pathology of lichen planus showing typical changes, with a band of lymphocytes and histiocytes in
the subepidermal region (lichenoid band) and epidermal thickening with hypergranulosis, but a sawtooth pattern
of erosion in the basal epidermal region. (b) Detail of the pathology of lichen planus showing the basal epidermal
region with erosion, cytoid bodies and a dense lymphocytic inltrate.
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Summary
Immunouorescence studies show a dense, ragged band of brin at the dermoepidermal junction and clumps of IgM deposit.
The basic process is thought of as an immunological attack on the basal layer;
the presence of inammatory cells and the other epidermal alterations are
believed to be secondary events.
TREATMENT
The disease mostly remits spontaneously, so that most patients require very little
treatment. Weak topical corticosteroids may be helpful in relieving the pruritus.
When patients are severely affected with a generalized eruption, systemic corticosteroids are sometimes helpful, as is the oral retinoid acitretin.
Summary
Psoriasis
Psoriasis is a genetically determined, persistent
and/or recurring inammatory dermatosis, which
occurs in 12 per cent of the population. It usually
starts between the ages of 15 and 25, but in some
patients it develops in the 60s.
It is characterized by raised, red, rounded, scaling
patches of variable size that tend to occur on the
elbows, knees, scalp and other extensor
surfaces.
Nail involvement occurs in many patients and is
characterized by thimble pitting, subungual debris
and areas of discoloration.
Variants include guttate psoriasis with myriads of
tiny psoriatic patches, exural psoriasis, generalized
pustular psoriasis and a localized form of pustular
psoriasis occurring on the palms and soles, and
erythrodermic psoriasis.
Psoriasis needs to be distinguished from other red
scaling conditions, including eczematous disorders
such as seborrhoeic dermatitis, lichen simplex
chronicus and discoid eczema, ringworm infections
and neoplastic disorders such as Bowens
disease and supercial basal cell carcinoma.
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Lichen planus
Lichen planus is a self-limiting, not uncommon
inammatory disorder of skin and mucosae
of unknown origin, but with a prominent
immunopathogenetic component.
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C H A P T E R
10
149
Rosacea
162
Perioral dermatitis
168
Summary
169
Acne
Acne is one of the commonest skin disorders if not the commonest. It has been
estimated that 70 per cent of the population have some clinically evident acne at
some stage during adolescence!
DEFINITION
Acne (acne vulgaris) is a disorder in which hair follicles develop obstructing
horny plugs (comedones), as a result of which inammation later develops
around the obstructed follicles, causing tissue destruction and scar formation.
CLINICAL FEATURES
The lesions
The earliest feature of the disorder is an increased rate of sebum secretion, making the skin look greasy (seborrhoea). Blackheads or comedones usually accompany the greasiness. They often occur over the sides of the nose and the forehead,
but can occur anywhere (Fig. 10.1). Comedones are follicular plugs composed
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of follicular debris and compacted sebum. They have pigmented tips from the
melanin pigment deposited by the follicular epithelium at this level (Fig. 10.2).
Accompanying the visible comedones are numerous invisible comedones, many
of which do not have pigmented tips.
Inamed, reddened papules develop from blocked follicles. These are often
quite tender to the touch and may be set quite deep within the skin (Fig. 10.3).
Sometimes they develop pus at their tips (pustules), but these may also arise independently. In a few patients, some of the papules become quite large and persist
for long periods they are then referred to as nodules.
In severely affected patients, the nodules liquefy centrally so that uctuant cysts
are formed. In reality, the lesions are pseudocysts, as they have no epithelial lining. This type of severe acne is known as cystic or nodulocystic acne and can be
very disabling and disguring.
When the large nodules and cysts eventually subside, they leave in their wake
rm, brotic, nodular scars, which sometimes become hypertrophic or even
keloidal (Fig. 10.4a). The scars are often quite irregular and tend to form bridges
(Fig. 10.4b). Even the smaller inamed papules can cause scars and these tend to
be pock-like or are triangular indentations (ice-pick scars: Fig. 10.5).
There is a very rare and severe type of cystic acne known as acne fulminans
in which the acne lesions quite suddenly become very inamed. At the same time
the affected individual is unwell and develops fever and arthralgia. Laboratory
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Acne
(a)
(b)
Figure 10.4 (a) Nodular scars in acne. These lesions developed following the
resolution of inamed acne papules. (b) Hypertrophic scarring in a bridging pattern.
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SITES AFFECTED
Any hair-bearing skin can develop acne, but certain areas are much more
prone than others (Fig. 10.6). These acne-prone areas tend to have hair follicles
with small terminal hairs and larger sebaceous glands (sebaceous follicles). The
face and particularly the skin of the cheeks, lower jaw, chin, nose and forehead are
usually affected. The scalp is not involved, but the back of the neck, front of the
chest, the back and shoulders are all favoured areas for the development of
lesions.
In patients with severe acne, it is quite common for other areas to be affected,
including the outer aspects of the upper arms, the buttocks and thighs.
CLINICAL COURSE
For most of those affected, the disorder is annoying and may be troublesome, but
is not of enormous signicance because it is limited in extent and only lasts a few
months or at the most a year. For the unfortunate few, the condition is a disaster,
as it is disguring, disabling and persistent, with wave after wave of new lesions.
Although the natural tendency is for resolution, it is difcult to know in any individual patient when the condition will improve. The majority have lost their acne
by the age of 25 years, but some tend to have the occasional lesion for very much
longer. In some women there is a pronounced premenstrual are of their acne
some 710 days before the menses begin.
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Acne
(a)
(b)
Acne improves in the summertime and sun exposure seems to improve the
condition of many patients. However, the heat does not produce improvement
and, indeed, can make it much worse. Soldiers with acne in hot, humid climates
often become disabled by it suddenly worsening, with large areas of skin covered
by inamed and exuding acne lesions, and have to be evacuated home or to a
cooler climate.
EPIDEMIOLOGY
Some 70 per cent of the population develop some clinically evident acne at some
point during adolescence and early adult life, but perhaps only 1020 per cent
request medical attention for the problem. This proportion varies in different
parts of the world, depending on the racial mixture, the afuence and the sophistication of medical services.
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The variations in incidence in different ethnic groups have not been well characterized, although it does appear that Eskimos and Japanese suffer less from acne
than do Western Caucasians.
Onset is usually at puberty or a little later, although many patients do not
appear troubled until the age of 16 or 17 years. Men appear to be affected earlier
and more severely than women. Older age groups are not immune and it certainly
is not rare to develop acne in the sixth, seventh or even eighth decade.
Acne lesions sometimes appear on the cheeks and chin of infants a few weeks
or months of age and even a little later than that (Fig. 10.7). This infantile acne is
usually trivial and short lived, but can occasionally be troublesome.
Androgens provide the normal drive to the sebaceous glands. It is the increased
secretion of these hormones that is responsible for the increased sebum secretion
at puberty. When given therapeutically for any reason, they can also cause an
eruption of acne spots.
Glucocorticoids, such as prednisolone, when given to suppress the signs
of rheumatoid arthritis or some other chronic inammation, can also induce
troublesome acne (Fig. 10.8). Why this should be so has never been adequately
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Acne
explained. Glucocorticoids do not seem to increase the rate of sebum secretion, and the acne that results is curiously monomorphic in that sheets of acne
lesions appear (unlike ordinary acne) all at the same stage of development.
Interestingly, corticosteroid creams can, uncommonly, also cause acne spots at the
site of application.
Oil acne
Workers who come into contact with lubricating and cutting oils develop an acnelike eruption at the sites of contact, consisting of small papules, pustules and
comedones. This is often observed on the fronts of the thighs and forearms, where
oil-soaked overalls come in contact with the skin. A similar acneiform folliculitis
sometimes arises at sites of application of tar-containing ointments during the
treatment of skin diseases (Fig. 10.9).
Some cosmetics seem to aggravate or even cause acne. This is because they
sometimes contain comedo-inducing (comedogenic) agents, such as cocoa butter
and derivatives and some mineral oils, that can induce acne. This cosmetic acne is
less of a problem now that cosmetic manufacturers are aware of it (Fig. 10.10).
Chloracne
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This disorder is most often seen in young women. Small acne spots around the
chin, forehead and on the jaw line are picked, squeezed and otherwise altered by
manual interference. The resulting papules are crusted and often more inamed
than routine acne spots. Often, the patients have little true acne and the main cosmetic problem is the results of the labour of their ngers!
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Acne
What do we believe is the sequence of events? In the rst place, patients with
acne have a higher rate of sebum secretion rate (SER) compared to matched
control subjects and, furthermore, there is some correlation between the extent of
the increase in the SER and the severity of the acne.
Acne rst appears at puberty, at which time there is a sudden increase in the
level of circulating androgens. Eunuchs do not get acne, and the administration of
testosterone provokes the appearance of acne lesions. Sebaceous glands are predominantly androgen driven and few other inuences are as important.
Follicular obstruction also plays an important role. Comedones are early lesions
and microscopically it is commonplace to nd horny plugs in the follicular canals.
Changes have been described in the follicular epithelium suggesting that there is
abnormal keratinization at the mouth of the hair follicle.
Pathogenic bacteria are not found in acne lesions and are not involved in
the pathogenesis. It is possible, nonetheless, that the normal ora has a role
to play. The ora consists of Gram-positive cocci the micrococci (also known
as Staphylococcus epidermidis) and Gram-positive bacteria Propionibacterium
acnes. In addition, there are also yeast-like micro-organisms known as Pityrosporum
ovale. The Propionibacteria are microaerophilic and lipophilic, so that they are
ideally suited to living in the depths of the hair follicle in an oily milieu, and it is
not surprising that they increase in numbers during puberty when their food
supply, in the form of sebum, increases. The normal follicular ora may be
responsible for hydrolysing the lipid esters of sebum, liberating potentially irritating fatty acids. The constituents of sebum and of skin surface lipid (after bacterial hydrolysis) are given in Table 10.1.
How can these observations be linked? An acceptable hypothesis is set out in
Figure 10.12, in which it is suggested that the important inammatory lesions of
acne are the result of follicular rupture.
TREATMENT
Typically, unasked for advice from the family is given in which the sufferer
is blamed in one way or another for having the disorder and accused of doing
too much of one thing or not enough of the other. Consequently, many forms
of familial or folk treatments seem to be more in the nature of punishments
than anything else. Dietetic and social restrictions are typical, as is more frequent
washing, which is another tactic adopted by well-meaning but misguided family
and friends.
Fortunately, most acne patients improve spontaneously after a few months.
Those who do not, nd their way to the pharmacist and purchase preparations
containing benzoyl peroxide or other antimicrobial compounds, or sulphur or
salicylic acid. Many with milder degrees of acne will be helped by these medications. It is only those with resistant, recalcitrant and more severe types of acne
who reach the physician. Perhaps only 10 per cent of those with clinical acne in
the UK see their practitioner.
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Comedone
Irritation of follicular wall
Increased lipolysis
Ruptured wall
Follicle lumen
Increased microflora
Inflammation
Sebaceous gland
Basic principles
reducing the bacterial population of the hair follicles to cut down the hydrolysis of lipids (antimicrobial agents)
encouraging the shedding of the follicular horny plugs to free the obstruction
(comedolytic agents)
reducing the rate of sebum production, either directly by acting on the sebaceous glands or indirectly by inhibiting the effects of androgens on the sebaceous
glands (anti-androgens)
reducing the damaging effects of acne inammation on the skin with antiinammatory agents (Table 10.2).
General measures
Patients with acne are often depressed and may need sympathetic counselling and
support. There is no evidence that particular foodstuffs have any deleterious effect
or that washing vigorously will help remove lesions. These and other myths
should be dispelled and replaced with a straightforward explanation of the nature
of the disorder, its natural history and treatment.
Topical treatment
Currently, the most popular form of topical preparation is a gel, cream or alcoholbased lotion.
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Acne
Oral
Comedolytic
Antimicrobial
Sebum suppressive
Benzoyl peroxide
Tretinoin
Tetracycline
Isotretinoin
Tetracycline
Isotretinoin
Minocycline
Erythromycin
Adapalene
Doxycycline
Cyproterone and
ethinylestranol
Erythromycin
Spironolactone
Clindamycin
Azelaic acid
Topical retinoids
These are comedolytic. Tretinoin-containing preparations are not bactericidal,
but are nonetheless effective. The cis-isomer of tretinoin isotretinoin is also
used successfully for the treatment of acne. Adapalene is a recently introduced,
effective topical retinoid that is also useful.
The side effects from the use of retinoid preparations include some pinkness
and slight scaling of the skin surface, especially in fair, sensitive-skinned individuals. For the most part, this dryness of the treated area is tolerable and decreases
after continual usage. It is less marked with adapalene.
Sulphur (as elemental sulphur 210 per cent) has been used traditionally as a
treatment for acne. It seems to be helpful for some patients, but has dropped out
of fashion. Its efcacy probably depends on both its antimicrobial action and its
comedolytic activity.
Other agents employed to remove blackheads include abrasive preparations.
These contain particles of substances such as aluminium oxide or polyethylene
beads, which literally abrade the skin surface and liberate the comedones.
Topical antibiotics
Erythromycin (12 per cent) and clindamycin (2 per cent) preparations are quite
effective for mild and moderate types of acne. Tetracycline preparations (2 per
cent) are slightly less effective. Fortunately, these antibiotics have a low tendency
to sensitize and are not often responsible for allergic contact dermatitis, although
they may cause a minor degree of direct primary irritation.
Other antimicrobial compounds
Bacterial resistance to erythromycin frequently develops and may prove a problem in the future.
Systemic treatment
Antibiotics
Tetracyclines
Systemic tetracyclines have been the sheet anchor of treatment for moderate and
severe acne for many years. Patients with many papular lesions involving several
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sites are suitable for systemic tetracyclines. It is usual to start treatment with a
dose of 250 mg t.i.d. or 6-hourly, and then, when there is a response, to reduce the
dose to that required to keep the patient free of new lesions. The improvement
usually begins 48 weeks after starting treatment and continues over the next 23
months. Some 70 per cent of patients can be expected to improve on this regimen.
Treatment may have to be maintained for several months or, exceptionally, even
longer. With tetracycline and oxytetracycline, the drug should be given 30 minutes
before a meal to prevent interference with absorption. The newer minocycline and
doxycycline are given in smaller doses (50 mg or 100 mg) once or twice per day
and their absorption does not seem to be affected by food.
Side effects with the tetracyclines are few and not usually serious. Gastrointestinal
discomfort and diarrhoea occasionally occur. Photosensitivity was mainly a problem with older, now no longer used, analogues. Fixed drug eruption and, rarely,
other acute drug rashes develop. Minocycline can cause a dark-brown pigmentation
of the skin or acne scars or acral areas on the exposed part of the skin after longcontinued use in a small number of patients.
Tetracyclines must not be given to pregnant women, as they are teratogenic,
and must not be given to infants, as they cause a bone and tooth dystrophy in
which these structures become deformed and discoloured.
Erythromycin
The efcacy of erythromycin in acne is similar to that of the tetracyclines. The
starting dosage is 250 mg 6-hourly for the rst few weeks, with reduction after a
response has begun. Subsequently, management is as for the tetracyclines. Side
effects are usually minor and restricted to nausea.
Other antibiotics and antimicrobials
Clindamycin, the quinolines and the sulphonamides are other drugs that have
been used systemically for acne. None is more effective than the tetracyclines, but
they may be suitable for patients who are either intolerant or who no longer
respond to the tetracyclines or erythromycin. Side effects are more common and
sometimes of a serious nature (e.g. blood dyscrasias).
Isotretinoin (13-cis-retinoic acid)
The large majority of patients with acne will respond to topical or some combination of topical and systemic drugs. However, some severely affected patients
may not, and for them there is another drug that can offer relief. This agent is the
retinoid isotretinoin (the same cis-isomer of tretinoin used topically). It reduces
sebum secretion by shrinking the sebaceous glands and may also alter keratinization of the mouth of the hair follicle and have an anti-inammatory action.
It is given in a dose of 0.51.0 mg/kg body weight per day, usually for a
4-month period. The response after a few weeks is to inhibit new lesions in more
than 80 per cent of patients. Patients with many large cystic lesions affecting the
trunk as well as the head and neck region take longer to respond and may need
more than one 4-month course.
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Acne
Unfortunately, toxic side effects are frequent. They range from the trivial, of
which the most common is drying and cracking of the lips, to the very serious,
which include teratogenicity, hepatotoxicity, bone toxicity and a blood lipidelevating effect. The teratogenic effects are very worrisome, as the acne age group
is almost identical to the reproductive age group. The effects on the fetus include
facial, cardiac, renal and neural defects and are most likely to arise if the drug is
taken during the rst trimester. Some 3050 per cent of pregnancies during which
the drug was taken have been affected. Because of this, it is strongly recommended
that if it is planned to prescribe isotretinoin for women who can conceive, effective contraceptive measures must also be planned and used during and for 2 months
after stopping the drug.
Hepatotoxicity is rare, although a small rise in liver enzymes is common. A rise
in triglycerides and cholesterol, such that the ratio of very low-density lipoproteins to high-density lipoproteins is increased, regularly occurs, and overall there
is a 30 per cent rise in lipid levels. This is not likely to be a problem for most
patients with acne, but may be for older patients. The same is true for the bone
toxicity. A variety of bone anomalies have been described, including disseminated
interstitial skeletal hyperostosis and osteoporosis, but these are not likely to be a
problem for acne subjects. The drug has also been accused of causing severe
depression, leading to suicide in some cases. The evidence for this is not strong, as
severe acne patients are often depressed before starting treatment. Because of the
toxicities of this important drug it can only be prescribed from hospitals in the UK.
Case 9
Julia was 15 when she started to develop embarrassing acne. She had noticed
that her skin had been very greasy skin for the last few months. New spots
appeared every day and she spent hours in front of the mirror trying to squeeze
out blackheads and get rid of pustules. It made her quite depressed and matters
were made worse by her parents telling her that she didnt wash her face enough
and that going to discos didnt help her skin. Fortunately, her GP was more
sympathetic and prescribed a benzoyl peroxide preparation and oral doxycycline,
which made a big improvement after about 6 weeks.
Anti-androgens
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Rosacea
DEFINITION
Rosacea is a chronic inammatory disorder of the skin of the facial convexities,
characterized by persistent erythema and telangiectasia punctuated by acute
episodes of swelling, papules and pustules.
CLINICAL FEATURES
Sites affected
The cheeks, forehead, nose and chin are the most frequently affected areas, making a typical cruciate pattern of skin involvement (Fig. 10.13). The exures and
periocular areas are conspicuously spared. Uncommonly, the neck and the bald
area of the scalp in men are also affected. Sometimes only one or two areas are
affected, and this makes diagnosis quite difcult.
The lesions
The most characteristic physical sign is that of persistent erythema, often accompanied by marked telangiectasia (Fig. 10.14). The disorder may not progress
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Rosacea
(a)
(b)
beyond this erythemato-telangiectatic state but, even if it does not, the bright red
face causes considerable social discomfort and often marked depression. Such
patients also complain of frequent ushing at the most trivial stimuli.
Superimposed on this persistent background of erythema are episodes of
swelling and papules, which develop for no very obvious reason (Fig. 10.15). The
papules are a dull red, dome shaped and non-tender, in contrast to acne, in which
they tend to be irregular and tender. Pustules also occur, but are less frequent than
in acne; blackheads, cysts and scars do not.
DIFFERENTIAL DIAGNOSIS
Any red rash of the face may be confused with rosacea (Table 10.3).
Papular rashes of the face seem to cause most problems. Acne occurs in a
younger age group and is usually distinguished by the greasy skin, comedones and
scars as well as lesions on sites other than the face. However, in some patients, the
presence of persistent erythema can make differentiation quite difcult. Perioral
dermatitis (see page 168) should not be difcult to differentiate, as this disease is
mainly distributed around the mouth and there is no background of erythema.
Systemic lupus erythematosus may supercially resemble rosacea, become of the
symmertrical buttery erythema but there are no symptoms of systemic disease
in rosacea. Dermatitis of the face (including seborrhoeic dermatitis) is marked by
scaling, which is not characteristic of rosacea.
Polycythaemia rubra vera gives the face a plethoric appearance. The carcinoid syndrome is characterized by reddened areas on the face in the same
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Positive discriminants
Skin disorders
Acne
Seborrhoeic dermatitis
Perioral dermatitis
Systemic disorders
Systemic lupus
erythematosus
Dermatomyositis
Carcinoid syndrome
COMPLICATIONS
Rhinophyma
This occurs mainly in elderly men, although it occasionally occurs in women too.
The nose becomes irregularly enlarged and craggy, with accentuation of the pilosebaceous orices (Fig. 10.16). At the same time, the nose develops a mauve or
dull-red discoloration with prominent telangiectatic vessels coursing over it (Fig.
10.17). Popular names for this include whisky-drinkers nose and grog blossom,
but it is not due to alcoholism.
Lymphoedema
Some 3050 per cent of patients with acute papular rosacea have a blepharoconjunctivitis. This is usually mild, but some patients complain bitterly of soreness and
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Rosacea
grittiness of the eyes. Some of this may be the result of keratoconjunctivitis sicca,
which appears to be quite common in rosacea. Styes and chalazion are also more
common in rosacea. Keratitis is a rare, painful complication occurring in men, in
which a vascular pannus moves across the cornea, producing severe visual defects.
NATURAL HISTORY
Rosacea tends to be a persistent disease and the tendency for patients to develop
episodes of acute rosacea remains for many years after appropriate treatment has
calmed down an attack.
EPIDEMIOLOGY
Rosacea is quite a common disorder, but its exact prevalence is not known and
varies in different communities. The disorder is essentially one of fair-skinned
Caucasians. It seems particularly common in Celtic peoples and in individuals
from northwest Europe. It is only occasionally seen in darker-skinned and Asian
skin types and is rare in black-skinned individuals. It has been claimed that it is
more common in women, but this may be merely a reection of the disorder
being of more concern to women.
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PATHOLOGY
There is no single pathognomonic feature, but there is a characteristic constellation of features in histological sections that makes skin biopsy a useful test when
the clinical diagnosis is uncertain. A feature common to all rosacea skin samples
is the presence of disorganization, solar damage, oedema and telangiectasia in the
upper dermis (Fig. 10.18). When there are inammatory papules, the blood vessels are encircled by lymphocytes and histiocytes, amongst which giant cell systems are sometimes found (Fig. 10.19). In rhinophyma, apart from abnormalities
in the brous dermis and inammation, there is also marked sebaceous gland
hyperplasia.
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Rosacea
Cold wind
Solar UV
Inherently
individual
susceptible
(Erythema and
telangiectasia)
DERMAL
DYSTROPHY
TELANGIECTASIA
Heat
Damage
to dermis
Damage to skin
sustained in acne
Pooling of blood
Endothelial damage
Inflammation
(Papules and
pustules)
Leakage of potentially
inflammatory substances
(swelling)
TREATMENT
Systemic treatment
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presumably because they cause even more upper dermal wasting and exposure of the
subpapillary venous plexus (Fig. 10.21).
Facial skin may be sore and uncomfortable in rosacea and the use of emollients
can give some symptomatic relief as well as discouraging the use of topical corticosteroids! Sunscreens are of help in preventing further solar damage. Preparations
of 0.751.5 per cent metronidazole in either a cream or gel base seem capable of
reducing the inammatory papules as efciently and as quickly as systemic tetracycline. Topical azelaic acid (20 per cent) has also been shown to be effective.
How systemic antibiotics, or metronidazole, systemic or topical, achieve their
effects in rosacea is not clear. Treatment with the pulsed dye laser can greatly
improve the erythema in rosacea.
Perioral dermatitis
DEFINITION
Perioral dermatitis is a not uncommon, inammatory disorder of the skin around
the mouth, characterized by the occurrence of micropapules and pustules.
CLINICAL FEATURES
Many minute, pink papules and pustules develop around the mouth, sparing the
area immediately next to the vermillion of the lips (Fig. 10.22). Lesions sometimes
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Summary
involve the nasolabial grooves and, in severely affected patients, also affect the skin
at the sides of the nose. There is no background of erythema, distinguishing the
condition from rosacea.
The condition develops insidiously and seems to persist until treated. Recurrence is uncommon.
Perioral dermatitis is most common in young women aged 1525 years, being
quite rare in men and in older women. Its exact incidence is unknown, but it is of
interest to know that it was rst recognized in the late 1960s, seemed quite common in afuent Western communities in the 1970s and then appeared to become
less frequently observed in the 1980s, reappearing once again in the 1990s. Many
have suspected that the use of topical corticosteroids is to blame. Patients usually
respond to a course of systemic tetracycline as for rosacea for a period of 48
weeks. No topical treatments are indicated.
Summary
Acne occurs in most individuals during adolescence.
It is characterized by increased sebum secretion
and the formation of comedones.
Comedones are dilated hair follicles containing
horny plugs, the tips of which are black due
to melanin (blackheads). These blocked follicles
often leak and may rupture, causing inammatory
papules and pustules, and when several are
involved, give rise to acne cysts (pseudocysts in
reality) form. The inammation causes tissue
destruction and hypertrophic, keloidal, pock-like
or ice-pick scars.
The face (cheeks, chin, forehead, lower jaw and
nose), back of the neck, back, shoulders and chest
are the commonest sites involved.
The disorder is not troublesome for most, but
discomforting and embarrassing for many, and a
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C H A P T E R
11
Wound healing
and ulcers
Principles of wound healing
171
173
Ischaemic ulceration
177
Decubitus ulceration
178
Neuropathic ulcers
179
180
182
Summary
182
Adequate supplies of nutrients and oxygen are required for efcient healing;
when the blood supply is compromised, healing is delayed. Vitamin C and zinc
deciencies are amongst the deciency states also associated with delayed
wound healing.
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E
FC
012 hours
DCT
BV
(a)
ME
F, MF, M
GT
12 hours4 days
BV
SC
(b)
BV
DC
F, M
410 days
(c)
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Aetiopathogenesis
Site(s)
Features
Venous ulcer
Ischaemic ulcer
Atherosclerosis in most
instances
Painful; occurring in
atrophic skin
Neuropathic ulcer
Decubitus ulcer
It has been estimated that between 0.5 and 1.0 per cent of the population of
the UK suffers from venous ulcers at any one time. The disorder is most often seen
after the age of 60 and women are more often affected particularly the multiparous. It is mostly a problem of the poor and underprivileged. Interestingly, it
does not occur with equal prevalence in all racial groups, for example it is rare in
Arabic peoples.
Pathology and pathogenesis
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(b)
(a)
Valves
Muscle pump
Muscle
pump
V
V
T
T
venules and, because of the changed pressure relationships at the tissue level,
exudation into the tissues and oedema.
This situation arises in the leg veins when the venous valves are faulty. Blood
leaks back through these faulty valves after being pushed towards the heart by the
muscle pump of the lower leg (Fig. 11.2). The valves become faulty because venous
thrombosis destroys them, but are sometimes congenitally faulty. Venous hypertension caused by the back pressure is transmitted back to the smaller supercial veins
via perforating veins, causing varicosities and telangiectasia (Figs 11.3 and 11.4).
The increased pressure at the venous end of the capillaries leads to transudation and the deposition of brin perivascularly (Fig. 11.4). The tissue oedema and
Figure 11.3 The results of venous hypertension the
gravitational syndrome. Note the pigmentation,
telangiectasia and visible varicosities.
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The earliest signs are of pitting ankle oedema and distended supercial long veins
in the lower leg. A network of smaller veins appears around the foot. Later, brownish discoloration develops and the swelling becomes rmer and eventually woody
to the touch because of the brosis (Fig. 11.5). Ulceration may occur at any stage,
usually after a minor injury that does not heal but steadily enlarges.
Venous ulcers are usually seen around the medial malleolus, but sometimes
occur elsewhere and are usually single (Figs 11.6 and 11.7). Large ulcers may
encircle the leg. The base of venous ulcers is often lined by a yellowish grey slough
and the edges are for the most part ush with the skin surface and irregular in
outline (Fig. 11.7).
Course and prognosis
Many ulcers heal, but may take many months to do so. Unfortunately, when healed,
they tend to recur. Some never completely heal, but run a remittent course.
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Complications
Infection. They may become severely infected with either Gram-positive cocci
or Gram-negative micro-organisms.
Bleeding. Uncommonly, large veins may rupture and cause severe bleeding.
Eczema. An eczematous rash is common in patients with venous ulcers. In twothirds to three-quarters of patients, this is the result of allergic contact hypersensitivity to one of the medicaments used in treatment (e.g. neomycin, Vioform)
or one of the constituents of the vehicle (e.g. lanolin or ethylene diamine; see
page 123). In a few patients, autosensitization is thought to occur in which sensitivity to the breakdown products from the ulcerated area develops. Venous
eczema develops on the opposite leg, the lateral aspects of the thighs and the
upper arms and at other scattered sites.
Malignant change. Rarely, squamous cell carcinoma or basal cell carcinoma
develops in long-standing lesions.
Anaemia. Patients with persistent ulcers often develop a normochromic
anaemia and are generally debilitated. The loss of protein, salts and metabolites
in the exudates from the open area and absorption of products of tissue degradation and bacterial activity are probably responsible.
Treatment
Elevation of the legs above the head level at regular periods during the day (two
1-hour periods).
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Ischaemic ulceration
Dressings
Non-adherent, non-toxic, non-sensitizing dressings should be used. Antibacterial
properties are also helpful. In addition, dressings should ideally be partially
absorptive and semi-occlusive to provide high humidity at the wound interface.
This promotes re-epithelialization. Hydrocolloid dressing materials, gels and some
paste bandages are suitable. Tulle dressings are also acceptable.
Topical treatments
The ulcer base may be irrigated with normal saline, dilute potassium permanganate solution or very weak chlorhexidine or hypochlorite solutions. Many traditional agents are damaging to the healing tissues and must not be left in contact
with the wound surface.
Surgery
Split skin fragment grafts may speed ulcer healing in the short term, but may not
improve the long-term outlook. Grafts with skin cultivated in vitro have also been
used with some success. Surgical management of the incompetent veins may assist
in some cases.
Case 10
Andrew was fed up. At the age of 79 he had been all through the 193945 war
without serious injury, but now he had a large, non-healing ulcer on his right ankle
(just above the medial malleolus). It hurt quite a bit, but he found that the oozing
and unpleasant smell it caused were even more troublesome. Andrew had
the ulcer for 3 months and wanted to get rid of it. His ankles were swollen and
there was some brown discoloration around both of them. The dermatologist told
him that the ulcer was due to the veins not draining the blood back from his legs
efciently. Andrew was told to lose weight, to use elasticated stockings and to
elevate his legs for at least 2 hours per day. Arrangements were made for the
district nurse to dress his ulcer three times a week with a non-adherent dressing,
and he was happy when it started to heal a few months later.
Ischaemic ulceration
Ulceration due to ischaemia is a common clinical problem, though less often seen
than that due to venous hypertension.
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PATHOGENESIS
Atherosclerosis accounts for the majority of cases. This affects major vessels and
mostly occurs gradually, so that the ulceration occurs in chronically ischaemic
skin. Embolism may cause acute ulceration and gangrene.
Diabetes predisposes to atherosclerosis and impairs wound healing, making
the problem particularly common. Disease of the medium-sized or small blood
vessels also causes ulceration in allergic vasculitis.
It should be noted that ischaemic and venous ulcers are often due to both
processes, although one predominates, as venous hypertension and atherosclerotic arterial disease are common and often coexist.
CLINICAL FEATURES
Ischaemic ulcers are painful and irregular, occurring anywhere around the feet or
lower legs. The skin around the ulcerated area is pale, cool, smooth and hairless.
Light pressure with a nger on the skin makes it a deathly white and the pink
colour takes longer to return than normal.
TREATMENT
Medical treatment is only helpful in the earliest and mildest cases. Keeping the
affected part warm and protecting it from injury are important. Peripheral vasodilating drugs are only marginally useful (e.g. pentaerythritol tetranitrate, glyceryl
trinitrate, isosorbide dinitrate, nifedipine). Drugs promoting vascular ow, such
as hydroxyethyl rutosides and oxpentifylline, are rarely helpful.
Sympathectomy removes sympathetic vasoconstrictor tone and causes some
vasodilatation, but rarely results in much clinical benet. Of greater help is
endarterectomy, either by open surgical technique or percutaneously, or arterial
grafting.
Decubitus ulceration
These lesions are the result of localized ischaemia due to long-continued pressure
on skin at contact points with bedclothes and occurs in the unconscious or paralysed patient.
CLINICAL FEATURES
Classically, ulcers occur over the sacrum or ischial regions (Fig. 11.8), the heels,
the back of the head, the scapulae and the elbows. The ulcers are often deeply
penetrating and sloughy.
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Neuropathic ulcers
Neuropathic ulcers
Neuropathic ulcers result from repeated, inadvertent injury to hypoanaesthetic or
anaesthetic areas of skin subsequent to nerve injury. They are most often seen in
diabetes in the UK and Europe, but leprosy is a common cause in some parts of
the world.
CLINICAL FEATURES
These lesions may be very deeply penetrating. They occur mostly on the soles of
the feet, but may also be seen elsewhere on the foot (Fig. 11.9).
TREATMENT
Local treatment is unlikely to make any impact on these lesions. The only effective treatment is to protect the damaged area with padding and appliances and,
if possible, to restore sensation to the anaesthetic area.
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The disorder may occur in the course of ulcerative colitis, Crohns disease,
rheumatoid arthritis or myeloma, although in about half the cases no predisposing cause is found. It has been suggested that the tissue destruction is caused by a
vasculitis, although it is difcult to nd evidence of this.
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Treatment
VASCULITIC ULCERS
Ulcers may develop in the course of a disorder in which small blood vessels become
inamed and thrombosed (vasculitic). Rheumatoid vasculitis is one such condition in which ulceration may occur. Ulcers often occur on the legs (Fig. 11.11), but
may develop anywhere. They may start from a patch of purpura. Treatment is
directed towards the underlying illness.
HAEMATOLOGICAL CAUSES
Leg ulcers are more common in patients with sickle cell disease and idiopathic
thrombocytopenic purpura.
INFECTIVE CAUSES
Tuberculosis, tertiary syphilis and deep fungus infections can all result in persistent ulcers.
ARTERIOVENOUS MALFORMATION
Shunting of the blood at deeper levels may deprive the overlying skin and cause
ulcers (Fig. 11.12).
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MALIGNANT DISEASE
This is an uncommon, but important to recognize, cause of persistent ulceration.
The lesions are usually squamous cell carcinoma or basal cell carcinoma. They
have raised edges and are slowly but relentlessly progressive.
Summary
Non-healing may be due to inadequate nutrition,
infection or a congenital disorder (e.g. factor XIII
deciency). Leg ulcers are a very common cause of
disability. The commonest cause of leg ulcers is
venous hypertension due to faulty venous valves,
which is most often seen in the elderly. The
inadequate venous return causes venous
hypertension, resulting in oedema, extravasation of
blood into the tissues, thickening of the small
vessels, perivascular deposition of brin and
inammation leading to brosis.
Oedema, telangiectasia and brown discoloration
usually precede ulceration. Such ulcers are sloughy
and of varying size. They occur around the medial
malleolus and tend to persist, but elevation,
compression bandaging and weight reduction are
important in their treatment. Dressings should be
non-adherent, absorptive and non-toxic.
Ischaemic ulceration is due to inadequate blood
supply to the skin and usually the result of
atherosclerosis. Often, there is an element of
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C H A P T E R
12
183
184
186
188
188
192
194
197
Leiomyoma
198
Neural tumours
199
Lipoma
200
200
201
Cysts
202
204
Summary
205
Introduction
The many cell and tissue types in skin is responsible for the enormous number of
benign tumours that may arise from it. Despite the large number of such lesions,
they have a limited number of clinical appearances and, because of this, accurate
clinical diagnosis is difcult. The treatment of all the lesions included is discussed
together at the end of the chapter.
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Comment
Seborrhoeic wart
Viral wart
Solar keratosis
Epidermal naevus
They usually cause no symptoms, but patients complain that they catch in
clothing and are unsightly. They may also irritate and, less frequently, become
inamed and cause soreness and pain.
Histologically, there is epidermal thickening, the predominant cell being rather
like the normal basal epidermal cell. Surmounting the thickened epidermis there is
a warty hyperkeratosis whose arrangement has been likened to a series of church
spires (Fig. 12.3). Within the lesion are foci of keratinization and horn cysts.
EPIDERMAL NAEVUS
Epidermal naevus is the name given to a wide variety of uncommon, localized
malformations of the epidermis. Congenital in origin, they are classied as hamartomata and are usually present at birth.
Clinical appearance
Many epidermal naevi are arranged linearly and are warty. Sometimes they track
along a limb and adjoining trunk and are extensive and disguring. This type is
known as naevus unius lateris (Fig. 12.4). Histologically, there is regular epidermal thickening and hyperkeratosis, often in a church-spire pattern.
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VARIANTS
Beckers naevus is an odd type of hamartomatous lesion that develops in adolescence or early adult life. It usually occurs around the shoulders or upper arms, but
is not unknown elsewhere. A comparatively large area of skin is affected by a
brownish and sometimes hairy plaque (Fig. 12.5). It consists of hypertrophy of all
the epidermal structures, including the hair follicles and melanocytes.
Naevus sebaceous lesions are yellowish orange plaques on the scalp, which contain
hypertrophied and deformed structures of epidermal origin in various amounts.
They are either present at birth or shortly afterwards, and may enlarge, thicken and
develop other lesions in them, such as basal cell carcinoma in adult life (Fig. 12.6).
SYRINGOMA
Syringoma lesions are multiple, small, white or skin-coloured papules that occur
below the eyes (Fig. 12.7) in young adults. Uncommonly, they are also evident on
the arms and lower trunk. Histologically, there are tiny, comma-shaped epithelial
structures, some of which appear cuticle lined, forming microcysts (Fig. 12.8).
CYLINDROMA
This is a benign tumour arising from apocrine sweat glands that, like syringoma,
is often multiple. Smooth, pink and skin-coloured nodules and papules occur over
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Cylindroma
Syringocystadenoma
papilliferum
Nodular hidradenoma
Eccrine poroma
Eccrine spiradenoma
the scalp and face in young adults. Oval and rounded masses of basaloid epidermal cells surrounded by an eosinophilic band of homogeneous connective tissue
characterize the histological appearance.
NODULAR HIDRADENOMA
This is a rare benign tumour of sweat gland epithelium. It is usually solitary and
may be pigmented. Histologically, it consists of clumps of small epithelial cells
amongst which are duct-like structures.
ECCRINE POROMA
Eccrine poroma describes an eccrine sweat duct-derived tumour that arises predominantly on the palms and soles in adults. Histologically, the lesion appears
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contiguous with the surface epidermis and consists of basaloid cells in which there
are cuticularly lined duct-like structures.
TRICHOEPITHELIOMA
Trichoepithelioma is more often multiple than solitary and usually occurs over
the scalp and face. Histologically, it consists for the most part of clumps of epithelial
cells and horn-lled cysts.
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Clinical features
Comment
Congenital/simple
Girdle
Acquired
Junctional
Macular, brown/black
Dermal cellular
Compound
Naevus spilus
Uncommon
Dysplastic naevus
syndrome
Juvenile melanoma
Blue naevus
Mongolian spot
Predominantly in Asians
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CONGENITAL NAEVI
These lesions, which are present at birth, are usually solitary and dark brown, and
are more than 1 cm2 in size. They are plaque-like or nodular (Fig. 12.11). They
share with the limb girdle naevus the increased tendency to malignant transformation. It has been suggested that 10 per cent of the larger congenital naevi develop
malignant melanoma.
The most deforming congenital melanocytic naevi are those that cover large
tracts of skin on the pelvic region and adjoining back (bathing trunk naevi) or
over the shoulder region and upper limb (cape naevi: Fig. 12.12). Histologically,
these lesions consist of numerous packets (theques) of naevus cells (Fig. 12.13),
which may be small and basophilic (lymphocytoid), large and less intensely staining (epithelioid) or spindle shaped. They may also coalesce to form naevus giant
cells or, after they have been present for many years, may show degenerative
changes, including fatty degeneration and calcication. Naevus cells tend to be
faceted together in a rather characteristic way.
ACQUIRED NAEVI
Acquired naevi appear after birth, usually during adolescence or young adult life.
Potential difculty arises when an adult notices a brown lesion for the rst time.
Has it been there for many years before being noticed? Or is it a new benign mole,
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(b)
(a)
Figure 12.13 (a) Pathology of congenital melanocytic naevus showing packets or theques of naevus cells, some of
which are naevus giant cells. (b) Many large naevus giant cells.
Comments
some other pigmented lesion, or a malignant melanoma? The differential diagnosis for this situation is given in Table 12.4.
JUNCTIONAL NAEVI
These are at, brown or black moles in which clumps of naevus cells can be
observed at the dermoepidermal junction (Fig. 12.14) nestling in dermal papillae.
It is presumed that this is the rst stage in the life cycle of the ordinary mole.
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elderly when there is little pigment, they are often misdiagnosed as basal cell
carcinomata.
COMPOUND NAEVI
These have the characteristics of a dermal cellular naevus, but there are areas of
junctional activity with foci of naevus cells at the dermoepidermal junction. It is
presumed that these lesions are intermediary in development between the junctional naevus and the dermal cellular naevus.
BLUE NAEVI
In the ordinary cellular blue naevus, the melanin pigment and the bulk of the
naevus cells are in the mid and deep dermis. The striking blue colour given by the
pigment is due to the red wavelengths being ltered out by the supercial dermis
and epidermis. This type of blue naevus is found over the scalp (Fig. 12.15) and
the back of the hands or feet.
The Mongolian spot is a type of blue naevus commonly found in Asiatics. It
occurs as a greyish discoloration over the sacral area in the newborn, becoming
less prominent in later life.
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The naevus of Ota and the naevus of Ito are due to spindle-shaped naevus cells
over the upper face and lower face and neck, respectively (Fig. 12.16).
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JUVENILE MELANOMA
This is a quite uncommon, benign lesion of childhood and adolescence. Although
usually solitary papules or small plaques, the lesions are occasionally multiple
(Fig. 12.18). The individual lesions are pink or orange and may have a corrugated
or peau dorange surface. Their name derives from their histological appearance,
which may look frighteningly like a melanoma to the uninitiated.
This is the popular name for the red discoloration at the back of the neck in a high
proportion of newborns. It fades in later childhood and seems to be due to
vasodilatation rather than to an excess of blood vessels.
PORT-WINE STAINS
These common vascular malformations may occur anywhere, but seem to be
most common on the face and scalp. The deep crimson colour (or port wine) is
distinctive and cosmetically very disguring (Fig. 12.19). The lesions contain
many dilated blood vessels but no other obvious histological abnormality.
The surface of the lesion becomes more thickened and rugose with age and
even develops polypoid outgrowths, adding to the grotesque appearance. When
on a limb, deep vascular malformations may also be present, which can cause limb
hypertrophy. Over the ophthalmic region, the obvious skin malformation of
blood vessels may be associated with an underlying meningeal angiomatous
malformation. When this combination of lesions is associated with epilepsy, the
disorder is known as the SturgeWeber syndrome.
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CAPILLARY ANGIOMA
The lesions are usually present at birth, but may develop in the rst few months of
life. They are raised, purplish nodules and plaques whose surface is often lobulated
(supposedly like a strawberry) and show an enormous range of sizes. The smaller
lesions have little functional signicance (Fig. 12.20) and usually atten or disappear at puberty. The larger lesions are very deforming and may cover quite a large
area of skin (Fig. 12.21). The larger lesions, particularly, may ulcerate after minor
trauma, presumably due to ischaemia of the overlying supercial dermis and overlying epidermis because of the shunting of blood between the larger, deeper vessels
of the angioma. Any bleeding can be stopped with gentle pressure and the eroded
area gradually heals with routine care. One other rare complication only occurs with
the largest of capillary angiomas. Blood platelets become sequestered in the abnormal vascular channels of the angioma, creating a consumption coagulopathy and
uncontrolled bleeding (KatzenbachMerritt syndrome). The bleeding can be dealt
with by administration of systemic steroids.
CAVERNOUS HAEMANGIOMA
This is a soft, compressible, mauvish-blue swelling composed of large vascular
spaces. This lesion shows little tendency to reduce in size in later life.
LYMPHANGIOMA CIRCUMSCRIPTUM
This lesion is a malformation of lymphatic channels, although there may also be
an associated blood vessel anomaly. The lesions usually have a deep component,
which it is almost impossible to eradicate surgically. Clinically, the malformation
is recognized as a diffuse skin swelling with what appears to be a cluster of tense
vesicles at the skin surface, with a frogspawn-like appearance (Fig. 12.22).
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ANGIOKERATOMA
There are several types of angiokeratoma, which all consist of a small, subepidermal vascular malformation surmounted by a hyperkeratotic epidermis. They may
occur as solitary red papules or, occasionally, as a crop of red spots over the scrotum (Fig. 12.23). When literally hundreds of tiny red papules develop over the
trunk in young men, the possibility of the very rare inherited metabolic abnormality known as angiokeratoma corporis diffusum must be considered.
CAPILLARY ANEURYSM
Figure 12.24 Senile
angioma on the trunk in a
man aged 63 years.
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PYOGENIC GRANULOMA
This odd lesion characteristically appears suddenly over a week or two and then
disappears after several weeks. Typically, it is a red, dome-shaped papule with a
glazed or eroded surface (Fig. 12.25), often on the ngers and toes. Histologically,
it consists of a matrix of oedematous, glassy connective tissue in which there
are numerous thin-walled vascular channels and a moderately dense, mixed
cellular inltrate. Its cause is unknown and it is certainly not due to pyogenic
micro-organisms.
HYPERTROPHIC SCAR
A scar is a reparative response to injury of some kind, accidental or surgical, or tissue destruction from an inammatory skin disorder, in which the tissue architecture cannot be entirely restored and the defect is made good with brous tissue.
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A hypertrophic scar is usually pink, smooth and variably raised (Fig. 12.27). The
excess scar tissue generally attens after some months or can be encouraged to
do so with topical corticosteroids and rm pressure bandaging.
KELOID SCAR
Like hypertrophic scar, this lesion arises in response to injury, but the response is
inappropriate to the often minor degree of trauma. It tends to occur in young
adults and adolescents, particularly women, and particularly around the shoulders, upper limbs and upper trunk. Some ethnic groups also appear more likely to
develop these lesions, black-skinned individuals being particularly prone.
Clinically, the lesions are raised and appear to send extensions into neighbouring
skin (Fig. 12.28). They show little tendency to regress, and surgical treatment
alone is usually insufcient, as they tend to recur in the scar. Corticosteroids,
interferons, radiotherapy and topical retinoic acid have all been tried, with
varying success. The use of silastic sheeting applied rmly to the affected area
has been claimed to be effective. The histological appearance of keloid scar,
with oedematous, pale connective tissue, suggests reversion to embryonic type of
collagen.
Leiomyoma
This is an uncommon benign tumour of plain muscle that arises either from arrector pilores muscle of hair follicles or from the smooth muscle of blood vessel walls.
It is mostly smooth surfaced, oval and bluish red in colour, varying in size from
1 cm to 3 cm in length and 0.5 cm to 1.5 cm in breadth. It may be spontaneously
painful, especially in the cold, and indeed can sometimes be seen to contract when
cooled. It can be confused histologically because of its spindle-shaped and strapshaped plain muscle cells, which may look like brous or neural tissue.
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Neural tumours
Neural tumours
These are, in fact, tumours of the connective tissue accompanying the neural
elements.
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at the apices of the axillae. There is a greatly increased risk of tumours affecting
the central and peripheral nervous systems as well as of tumours of sympathetic
tissue such as phaeochromocytoma. Genetic counselling of affected individuals is
of great importance.
NEURILEMMOMA
The neurilemmoma is an uncommon benign tumour of neural connective
tissue. The lesions vary in size and occur anywhere on the skin surface. Microscopically, they consist of thin, spindle-shaped cells arranged in a stacked or storiform manner.
NEUROMA
This rare, benign neural tumour is the most differentiated of all the neural connective tissue tumours and consists of well-formed nerve elements. It occurs at
the site of nerve injury and occasionally seems to arise spontaneously.
Lipoma
Lipomata are common, solitary or sometimes multiple, benign tumours of fat.
They may be enormous in size or only 12 cm in diameter and can occur anywhere. They are soft, skin-coloured and have poorly dened edges. Histologically,
they consist of mature fat cells.
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sclerosis. Pink or red, rm papular lesions develop (Fig. 12.31) in which vascular
brous tissue is found rather than an excess of sebaceous glands.
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Cysts
A cyst is an epithelium-lined cavity lled with uid or semi-solid material. The
distinguishing features of the commonly encountered cysts of the skin are summarized in Table 12.5.
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Cysts
Body site
Clinical features
Epidermoid
Virtually anywhere
Milium
Pilar
Sebocystoma
multiplex
Dermoid
EPIDERMOID CYSTS
These lesions are lined by epidermis and produce stratum corneum. They are
often surrounded by a tough, brous capsule, presumably stimulated by leakage
of the cyst contents. If these cyst contents nd their way into the dermis, considerable inammation results. The horny content may eventually degenerate,
forming a foul-smelling, semi-solid material. The fancied resemblance of this
to sebum has mistakenly led to the term sebaceous cysts for these lesions.
Epidermoid cysts may occur anywhere, but are most common over the head, neck
and upper trunk.
MILIA
Milia are tiny epidermoid cysts that occur at the sites of subepidermal blistering
as in porphyria cutanea tarda (see page 259) or spontaneously over the upper
cheeks and beneath the eyes. They are usually no larger than a pinhead and are
white. They contain tiny accretions of horn, which can be expressed by slitting the
thin epidermis over them with a needle tip.
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layer. Pilar cysts are usually multiple and are often genetically determined as an autosomal dominant trait. They occur on the scalp and on the scrotum in particular.
DERMOID CYSTS
Dermoid cysts are uncommon lesions that seem to contain embryonic epithelium
capable of forming a wide spectrum of tissue types. They may occur anywhere, but
are especially often found around the eyes as oval, rm, smooth-walled swellings.
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Summary
Case 11
Mrs J.G. was quite confused. Here she was, at the age of 57, developing more
moles on her back and abdomen! She already had ordinary acquired naevi on her
face and arms, as well as a large, pigmented patch of 2 cm2 diameter over her
upper back that she had been born with and that had been termed a congenital
mole. The new brown, warty spots over her abdomen and back irritated and
worried her and she didnt like the look of them. Her doctor told her that these
new pigmented lesions were nothing to worry about, but were common
seborrhoeic warts that could easily be removed by scraping them off curettage
under a local anaesthetic.
Summary
Seborrhoeic warts are extremely common, benign
epidermal tumours of ageing skin. They are usually
brownish and warty and may occur in large numbers
over the trunk. The differential diagnosis includes
epidermal naevus, solar keratosis, viral wart and,
most important of all, malignant melanoma.
Epidermal naevus is a localized, warty nodule or a
at, brownish patch over the shoulder or buttock
(Beckers naevus). Naevus sebaceous is another
type of epidermal naevus, which contains
sebaceous glands and maybe other adnexal
structures.
Benign tumours of sweat gland origin include
syringoma, cylindroma, nodular hidradenoma and
eccrine poroma.
Calcifying epithelioma of Malherbe (pilomatrixoma)
is a common, benign, hair follicle-derived tumour
occurring over the head and neck in young adults,
which eventually calcies.
Sebaceous gland hyperplasia is often seen in
elderly facial skin as one or several yellowish
nodules.
Melanocytic naevi (moles) are extremely common
developmental anomalies that contain many
immature melanocytes. Congenital naevi are
present at birth. They are usually more than 1 cm2
in diameter and dark brown in colour. Some, such
as those that cover large areas of the shoulder or
elsewhere on the trunk, are very deforming. A few of
these develop malignant melanoma.
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C H A P T E R
13
Malignant disease
of the skin
Introduction
207
207
219
224
Summary
226
Introduction
All forms of malignant disease of the skin are becoming more common. The reasons for this are:
The typical solar keratosis is a raised, pink or grey, scaling or warty hyperkeratotic
plaque or papule (Fig. 13.1). Solar keratoses are usually 25 mm in diameter,
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Table 13.1 Differential diagnosis of scaling and/or warty lesions on exposed sites
Diagnosis
Comments
Solar keratosis
Viral wart
Epidermal naevus
but may be much larger (Fig. 13.2). They are found on the exposed areas of skin
of elderly, fair-skinned subjects who show other signs of solar damage. Multiple lesions are the rule, and when a solitary solar keratosis is found, it may be
assumed that there is widespread solar damage and that further solar keratoses
will appear.
The differential diagnosis of small scaling or warty lesions of exposed skin sites
is given in Table 13.1. The clinical diagnosis of solar keratosis may be difcult and
with not quite typical lesions, an accuracy of more than 65 per cent is good, even
for experienced clinicians.
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dark-skinned subjects from the Middle East develop NMSC if they are excessively
exposed to the sun.
A small proportion of solar keratoses disappear spontaneously.
TREATMENT
Clearly, solitary lesions or small numbers of solar keratoses may be curetted off or
removed by cryotherapy with liquid nitrogen.
Chemotherapy is sometimes appropriate when there are very large numbers of
lesions present, for individuals who are seriously photodamaged, and three types
are available. The rst is topical 5-uorouracil as a 5 per cent ointment (Efudix,
Roche). This agent is applied daily or twice daily to the lesions over a 10-day or
14-day schedule. The lesions often become sore and inamed, and the patient
should be warned and given a topical corticosteroid to improve the symptoms.
This treatment is effective in some 50 or 60 per cent of cases and often saves considerable inconvenience and discomfort for elderly patients. Topical diclofenac
(Solaraze Shire) also appears to be quite effective. Imiquimod the immune
response-modifying agent may also be used for topical treatment.
Systemic retinoids (either acitretin or isotretinoin) may be used for patients
with multiple solar keratoses or other types of NMSC of several sites for whom
other types of therapy are unsuitable and who can tolerate the uncomfortable side
effects (see page 140). They are given in the same doses as for disorders of keratinisation, for periods of between 3 and 6 months. They reduce the size and number of lesions and reduce the rate of appearance of new lesions. Topical retinoids
are also employed and certainly have a prophylactic as well as a therapeutic effect
when used over long periods.
Intralesional injections of alpha-2B interferon, two or three times weekly
(1 000 000 units of alpha-2B on each occasion), for 3 or 4 weeks causes resolution
in 70100 per cent of lesions of solar keratoses or other types of NMSC. This
treatment is only suitable for very large lesions for which surgical or other destructive types of therapy are unsuitable.
The most typical type of lesion of Bowens disease is a raised, red, scaling plaque,
and lesions are often very psoriasiform in appearance. They are mostly present on
light-exposed areas of skin and are often seen on the lower legs of women (Fig.
13.3), which receive both incident UVR and UVR reected from the pavement.
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(b)
(a)
(c)
Figure 13.3 (a) Psoriasiform patch of Bowens disease on the lower leg of an elderly
woman. (b) Bowens disease on the cheek. (c) Pathology of Bowens disease showing
irregular thickening of the epidermis and cellular irregularity.
Single lesions are most common, but multiple lesions may occur. Lesions on the
trunk were common when arsenic was used as a treatment for psoriasis and other
chronic ailments. Individual lesions gradually enlarge and thicken and may eventually transform to squamous cell carcinoma.
Pathology and aetiopathogenesis
This is the term used for Bowens disease affecting the glans penis. It presents as a
red, velvety patch that slowly progresses, eventually transforming into a squamous
cell carcinoma if left untreated. Surgical excision of the affected area is the best
form of treatment.
The majority of lesions of squamous cell carcinoma are warty nodules or plaques
that gradually or, in some cases, rapidly enlarge to form exophytic eroded nodules or
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ulcerated plaques (Figs 13.4 and 13.5). The lesion is in most case solitary, although it
often occurs against a background of solar damage with multiple solar keratoses.
Metastases occur if the primary lesions are left untreated, spreading to local
lymph nodes, local skin sites and ultimately lungs, bone and brain.
The development of squamous cell carcinoma should be suspected in areas of:
severe photodamage
X-ray dermatitis
chronic heat injury such as erythema ab igne
chronic inammatory skin disease such as chronic discoid lupus erythematosus and chronic hypertrophic lichen planus.
There is marked epidermal thickening with cellular and nuclear heterogeneity and
atypia and evidence of abnormal mitotic activity. There is also evidence of focal and
inappropriate keratinization so that so-called horn pearls are formed (Fig. 13.6).
There is usually evidence of invasion of surrounding tissue by epithelial clumps and
columns.
Squamous cell carcinoma has to be distinguished from the massive but benign
epidermal thickening known as pseudoepitheliomatous hyperplasia seen in
hypertrophic lichen planus, prurigo nodularis and lichen simplex chronicus.
The factors in the aetiology of squamous cell carcinoma are as follows.
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other signs of photodamage as well as the index lesion, and intralesional interferon may be suitable for large lesions.
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Comment
Nodulocystic
Ulcerative
Pigmented
Morphoeic
Supercial
Clinical features
Nodulocystic. These are by far the commonest variety. Translucent or skincoloured, dome-shaped nodules (0.51.5 cm in diameter) slowly appear on
the skin and remain static for long periods, often for several years, before ulcerating (Fig. 13.9). They often have a telangiectatic overlying skin and may
be ecked with pigment. They usually occur as solitary lesions on the
exposed areas of the skin of the head and neck and are uncommon on the
limbs. Some 20 per cent occur on the trunk. They must be distinguished from
dermal cellular naevi, sebaceous gland hypertrophy and benign hair follicle
tumours.
Ulcerative. The nodulocystic type eventually breaks down to form an ulcer with
raised everted edges (Fig. 13.10). This type is known colloquially as rodent
ulcer.
Pigmented. Nodulocystic lesions may become quite darkly pigmented and are
then quite often mistaken for melanomas (Fig. 13.11).
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Morphoeic. These are often whitish, scar-like, depressed, rm plaques, and are
so named because of their supposed resemblance to localized scleroderma
(Fig. 13.12).
Supercial. These take the form of a variably sized, thin, pink, scaling plaques with
a well-dened edge (Fig. 13.13). If the edge is examined with a hand lens, a ne,
hair-like, raised margin can be discerned. They may be mistaken for Bowens
disease or even a patch of psoriasis. They often occur on the trunk and limbs.
All types of basal cell carcinoma gradually expand and invade and destroy local
tissue structures such as the ear, nose and eye. They metastasize rarely, but it is
difcult to know how often. However, when it is realized that basal cell carcinoma
is one of the most common human tumours and that metastasis has been
recorded in the literature only about 500 times, the proportion of lesions that do
metastasize must be extremely small.
Pathology and aetiopathogenesis
Clumps of small basophilic epidermal cells occupy the upper dermis, the outermost cells often being more columnar than the rest and arranged in a neat palisade
around the nodule (Fig. 13.14). Many mitotic gures may be seen amongst the
mass of basal cells, as may many degenerate cells it is thought that the slow
rate of growth is explained by cell death keeping pace with cell proliferation in
the tumour. In routine histological sections, it is common to nd a gap between the
clumps of tumour cells and the surrounding dermis, due to the dissolving out of
soluble glycoprotein-like material.
Most lesions of basal cell carcinoma are due to chronic solar exposure and
UVR damage, as they occur on light-exposed sites in photodamaged subjects.
However, a larger proportion occurs in younger, non-light-exposed, non-photodamaged subjects than solar keratoses or other forms of NMSC. The explanation
for this is uncertain, but it may be that some lesions arise from congenital malformations and are unrelated to UVR exposure.
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Epidemiology
The occurrence of basal cell carcinoma mirrors that of solar keratosis. As with
squamous cell carcinoma and other forms of photodamage, basal cell carcinoma
appears to be increasing in incidence.
Treatment
The majority of lesions can easily be excised. Smaller lesions can be curetted and
the base cauterized. Both these surgical ablative techniques result in a 95 per cent
cure. Larger lesions may be treated by radiotherapy after conrming the diagnosis
by biopsy.
Case 12
Liam was a farmer. He had spent most of his 63 years on the land and loved it.
Unfortunately, his skin did not. He had begun to notice lumps, bumps and
scaly patches a few years before, but now they really needed treatment. On his
bald scalp were multiple, scaling patches and small, warty lesions. These were
diagnosed as solar keratoses and were treated by a combination of curettage,
cryotherapy and topical 5-uorouracil ointment. Of more signicance were an
ulcerated, pearly plaque on one nostril and a thick, warty patch on his left ear.
The rst was a basal cell carcinoma and the latter was a squamous cell
carcinoma. Both received expert treatment from the local dermatologist, who was
a dab hand at removing such lesions.
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Clinical features
Multiple basal cell carcinomas may start to develop in the second decade of life
and erupt in large numbers in succeeding years. Less severely affected individuals
start to develop them later in life and develop fewer lesions. The lesions are mostly
pigmented and may occur anywhere on the skin surface. Small pits may be found
on the palms, but otherwise there are no skin abnormalities.
A series of skeletal anomalies is also present in the majority of patients, including mandibular cysts and bid ribs. In addition, patients have a high incidence of
ovarian, central nervous system and spinal tumours.
In recent years, considerable progress has been made in identifying the gene
responsible for this disorder.
Treatment
Individual lesions should be removed as necessary. When there are large numbers
present and new lesions are continuing to appear, the administration of systemic
retinoids will reduce the numbers of lesions and the rate of appearance of new
basal cell carcinomas (see page 140).
XERODERMA PIGMENTOSUM
Denition
The phenotypic expression depends on the particular genetic abnormality responsible, but in all types, pre-neoplastic and neoplastic lesions including solar keratoses, squamous cell carcinomas, basal cell carcinomas and melanomas develop
from childhood, and in the worst cases cause death in later adolescence or early
adult life. The development of skin cancers is accompanied by severe photodamage, resulting in a characteristic and pitiful appearance (Fig. 13.15). In one severe
recessive variety known as the de SanctisCaccione syndrome, there are also crippling neurological defects, including cerebellar ataxia and intellectual impairment.
Epidemiology and natural history
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Recently, the use of systemic retinoids has been shown to reduce the rate of development of new cancers and is now an important aspect of the management of
these patients.
There are many abnormal, often spindle-shaped, melanocytic clear cells at the
base of the epidermis and clumps of melanin pigment in the upper part of the
dermis. As the disease progresses, clumps of abnormal melanocytes appear, projecting into the dermis, and a dense inltrate of mononuclear cells develops.
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Main differentials
Comment
Lentigo maligna
Supercial spreading
malignant melanoma
Seborrhoeic wart,
pigmented basal cell
carcinoma, vascular
malformation,
melanocytic naevus
Acral lentiginous
melanoma
Melanocytic naevus,
vascular malformation
Malignant melanoma
growing vertically
downwards
Seborrhoeic wart,
pigmented basal cell
carcinoma, vascular
malformation,
melanocytic naevus,
pyogenic granuloma
Treatment
This is dictated by the size and exact site of the lesions. Often, they are of size and
site precluding surgical removal. In these instances, other locally destructive measures have been used, including curettage and cautery and radiotherapy. Careful
follow-up is required to detect the earliest signs of development of a frank melanoma.
MALIGNANT MELANOMA
Malignant melanoma is an invasive, neoplastic disorder of melanocytes in which
the tendency is for invasion either horizontally and upwards into the epidermis
(supercial spreading malignant melanoma, SSMM) or vertically downwards
(nodular malignant melanoma, NMM).
Clinical features
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skin surface. Any pigmented lesion that suddenly develops or any change in the
size, shape or colour of a pre-existing lesion should be suspected of being a malignant melanoma. Particular signs that are valuable in the recognition of these
lesions are irregularity in the margin or in the degree of pigmentation, and erosion or crusting of the skin surface (Fig. 13.17, Table 13.4). Itchiness of the lesion
is a not uncommon symptom in malignant melanoma.
One way in which this lesion may present is as a rapidly growing, nonpigmented nodule with an eroded surface, looking somewhat like a pyogenic
granuloma (Fig. 13.18).
Another unusual variety of malignant melanoma is the acral lentiginous
melanoma, which develops around the ngers or toes and sometimes subungually. This form has a particularly poor prognosis.
Late local signs are the development of satellite pigmented nodules and enlargement of the regional lymph nodes. Redness and other signs of inammation may
be present, but benign compound moles may also become inamed and inammatory change by itself is not common in malignant melanoma.
Although this is a potentially fatal disorder, the early stages are easily curable
and it is vitally important that every physician learns the signs of malignant
melanoma. Pigmented lesions can be very difcult to diagnose and there is no
shame in requesting another opinion.
The differential diagnosis includes melanocytic naevus (see page 188), pigmented basal cell carcinoma (see page 214), histiocytoma (see page 197) and vascular
malformation (see page 194).
The rate of progress of the disease seems largely determined by the inherent
biology of the malignant melanoma. When the lesion spreads horizontally
(SSMM), it tends to be noted and treated earlier than when the predominant direction of growth is vertically downwards (NMM). It is therefore not surprising that
the overall prognosis is much better for SSMM than for NMM. The single most
important determinant of prognosis appears to be depth of invasion into the
dermis (see below). Thus, patients with small lesions of less than 1 mm invasion
into the dermis have an expectancy of a 5-year survival rate in excess of 95 per cent.
Because of the signicance for prognosis of the depth of invasion into the dermis,
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Typically, there are clumps of abnormal melanocytes at the dermoepidermal junction. In SSMM, abnormal melanocytes tend to invade upward into the epidermis
and horizontally along the epidermis. In NMM, there are groups of abnormal cells
invading vertically downwards (Fig. 13.19). There is usually some accompanying
inammatory cell inltrate. It has to be said that the histological diagnosis of
melanoma may be difcult and should be left to the expert.
Solar UVR is believed to be the single most important causative factor, but, as up
to 50 per cent of lesions of malignant melanoma occur on non-sun-exposed sites,
other factors may play a role. The propensity for patients with the dysplastic mole
syndrome (see page 193) and large congenital melanocytic naevi to develop this condition suggests that developmental factors may also be involved in some instances.
There is some evidence that episodes of intense sun exposure over short periods,
with sunburn, may be very harmful. This could explain why malignant melanoma is
relatively common on areas of skin that are only occasionally exposed to the sun.
Epidemiology
Malignant melanoma is rare before puberty, but can occur at any age after that. It
is seen in all racial types, but is more common in fair-skinned, Caucasian types.
Acral lentiginous melanoma seems most frequent in black-skinned individuals
and subjects of Japanese or other Asian descent. The incidence has increased in all
countries that keep accurate gures and increases have been noted since records
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rst began. The rate of increase seems to be of the order of 7 per cent per annum.
The incidence is greatest in Queensland, Australia, and tends to be high in the hot,
sunny areas that have a large fair-skinned population of European descent.
Treatment
The treatment of choice is excision with a generous margin of normal skin. There
is debate concerning the width of the margin, but it should be at least 2 cm around
the lesion for a malignant melanoma of 1 cm diameter. There is also debate as to
whether or not regional lymph nodes should be removed prophylactically. The balance of opinion suggests not, provided that there is no clinical evidence of spread.
Metastatic disease responds poorly, if at all, to chemotherapy, but some decrease
in the size of metastatic deposits and occasional temporary remission have been
noted with combinations of antimetabolites and other anticancer drugs as well as
with retinoids, interferons and interleukin-2.
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over the dorsa of the feet and the lower legs. These lesions are usually accompanied by swelling of the lower legs. They are slowly progressive and may not appear
in other sites for many years. It has been estimated that the mean survival time
after the appearance of the rst lesions is approximately 12 years. Eventually,
lesions disseminate to other parts of the skin and to the viscera.
The rapidly progressive type occurs in patients with AIDS, particularly male
homosexuals, renal transplant patients and in areas of Africa notably Uganda.
The clinical manifestations are similar to those of endemic Kaposis sarcoma, but
are much more extensive and much more rapidly progressive.
Pathology and pathogenesis
The lesions consist of abnormal, slit-like vascular channels lined with spindleshaped cells, a mixed inammatory cell inltrate, haemorrhage and brosis. It is
believed that a herpes-type virus is involved in the causation.
Treatment
As the disorder appears to be multi-focal, cure does not appear possible at the
moment. However, radiotherapy keeps localized areas in check and systemic
interferon produces partial regression and remission in many patients. A new
topical retinoid, alretin, has also been shown to be effective.
Dematobromasarcoma
This is a slowly progressive neoplastic disorder of broblasts. It looks quite similar to a histiocytoma histologically and is an intracutaneous form of plaque clinically. Treatment is excision.
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The above sequence is the classical type of mycosis fungoides, and other less
common variants are occasionally seen.
SZARY SYNDROME
This is marked by an erythroderma that has a particular intense erythematous
colour, a picture sometimes referred to as lhomme rouge. It is accompanied by
thickening of the tissues of the face, neck and palms. It is also characterized by the
appearance of abnormal mononuclear cells circulating in the peripheral blood.
These cells, which are identied in the buffy coat, are large and have a large,
dense, reniform nucleus.
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Summary
Solar keratoses are localized areas of disorderly
epidermal growth and differentiation due to chronic
solar exposure. Typically, they are small, pink or
grey, warty or scaling lesions on the exposed skin of
fair-skinned, elderly subjects.
Solar UVR, heat, X-rays HPV infection, chronic
arsenic poisoning and immunosuppression are all
factors that may be involved in the causation of
solar keratoses. These lesions may be regarded as
pre-malignant, although they rarely progress and
often spontaneously remit.
Solar keratoses often respond to topical 5-uorouracil,
diclofenac or imiquimod. Systemic retinoids and
intralesional interferons have also been employed.
Bowens disease is a localized area of epidermal
neoplasia remaining within the epidermis, with even
greater cellular irregularity than a solar keratosis.
Red, scaling psoriasiform plaques on the legs are
typical. These plaques enlarge and thicken,
eventually transforming to squamous cell
carcinoma. Erythroplasia of Queyrat is Bowens
disease of the glans penis.
Squamous cell carcinoma is usually a warty nodule
or plaque that eventually ulcerates, invades local
structures, but metastasizes late. Histologically,
there is marked epidermal thickening and
irregularity, with cellular heterogeneity and focal
dyskeratosis. Solar UVR, heat, X-rays, HPV infection,
chemical carcinogens and chronic inammation may
be involved in the aetiology.
Keratoacanthoma arises suddenly as a solitary,
horn-lled crateriform nodule consisting of an
invaginated epidermal cup. It remits spontaneously
after 34 months.
Basal cell carcinoma is a very common, locally
invasive epithelial tumour of basaloid cells.
Nodulocystic types form pearly papules or plaques,
which eventually ulcerate. Some may be pigmented.
Supercial basal cell carcinoma spreads very slowly
as well-dened psoriasiform plaques. Morphoeic
basal cell carcinomas form rm plaques as the
cells evoke a brotic reaction. Histologically, areas
of mucoid degeneration amongst the basophilic
basal cell clumps are common.
Basal cell naevus syndrome is a rare
genodermatosis in which there are multiple
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C H A P T E R
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Old age
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Summary
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14
Infancy
FUNCTIONAL DIFFERENCES
In the neonatal period and early infancy, the skins defences are not yet fully
developed, and it is much more vulnerable to chemical, physical and microbial
attack. Apart from the depressed skin defences, the surface area to weight ratio is
higher than at other times and there is a greater hazard from increased absorption
of topically applied medicaments. For example, serious systemic toxicity can result
from the application of corticosteroids or a salicylic acid preparation. There is also
a greater rate of transepidermal water loss through intact, non-sweating skin in the
newborn compared to the adult, indicating immaturity of the skins barrier function.
This is easily conrmed by the use of a special water-sensor device known as the
evaporimeter.
During the early weeks of life, newborns possess the blood levels of hormones
found in the mother at birth. This may be of special signicance for the sebaceous
glands, which react to circulating androgenic compounds by enlargement and
increased sebum secretion.
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(b)
(a)
NAPKIN RASH
Several different skin disorders localize to the napkin area, which is perhaps not surprising when the physical assault that the wearing of napkins provides is considered.
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Infancy
This is the commonest type of napkin dermatitis. Red, glazed, ssured and even
eroded areas develop on the skin at sites in contact with the napkin (Fig. 14.2). The
exures are mostly spared, with the worst areas appearing on the convexities. There
is often a strong ammoniacal smell when the napkin is removed. This is due to the
release of ammonia from the action of the urease released from the faecal bacteria
on the urea in the urine.
The condition responds to nursing without napkins for 2 or 3 days, but if this is
not possible, more frequent napkin changes, the use of soft muslin napkins and
avoidance of abrasive towelling napkins help, as do efcient disposables that leave
the skin surface dry. An emollient washing agent and an emollient used 2 or 3 times
per day also help. Topical 1 per cent hydrocortisone ointment twice daily could be
used if the condition proves resistant.
Case 13
Casey was the rst child born to June. At the age of 412 months, a nasty,
bright-red rash developed on the convexities of her buttocks. This erosive napkin
dermatitis healed quite rapidly when June followed the advice she was given to
use only either good-quality, disposable napkins or soft, muslin napkins and to
change them more frequently. The use of an emollient also seemed to help.
Seborrhoeic dermatitis
Scaling, red areas develop, mainly in the folds of the skin, although the eruption
overows on to other areas in the napkin area. When the condition is severe and
angry, other sites such as the scalp, face and neck may be affected (Fig. 14.3). The
involved sites may also crack and become exudative. The same kind of care of the
napkin area as outlined above for erosive napkin dermatitis should be advised.
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In addition, the use of a weak topical corticosteroid in combination with broadspectrum antimicrobial compounds such as an imidazole (e.g. miconazole or
clotrimazole) should be used twice daily. The involvement of the yeast Candida
albicans in this form of napkin dermatitis has been claimed but not conrmed.
Napkin psoriasis
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Infancy
lukewarm water, with patting dry, rather than long-lasting hot scrubs with vigorous towelling afterwards. Weak topical corticosteroids only should be used 1 per
cent hydrocortisone and 0.1 per cent clobetasone butyrate are appropriate.
Preparations of 1 per cent hydrocortisone containing urea are helpful.
CRADLECAP
The newborn often develop yellowish scale over the scalp with very little other
abnormality apparent. This has no special signicance and usually disappears
after a few weeks. Application of olive oil or arachis oil with 2 per cent salicylic
acid and shampooing with baby shampoos hasten its removal.
INFANTILE ACNE
It is not uncommon for infants a few months old to develop seborrhoea, comedones, supercial papules and pustules on the face (Fig. 14.5). This infantile acne
has no special signicance, other than that maternal androgens have caused the
infants sebaceous glands to enlarge and become more active. When the disorder
develops in later infancy and is severe, the possibility of virilization due to an
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Old age
(a)
(b)
Treatment should be with an appropriate systemic antibiotic such as ucloxacillin. The skin should be managed as for a burn, and concern over heat loss,
dehydration and severe infection is necessary.
LIP-LICKING CHEILITIS
Children aged 48 years develop an area around the mouth which becomes sore,
red, scaly and cracked (Fig. 14.6). It is due to licking the lips and the skin around
the lips, which become irritated and dry and are then licked to moisten them,
making the situation worse. The treatment is to explain patiently the nature of the
problem to mother and child and to use an emollient on the affected area.
Old age
There is a growing acreage of elderly skin because of the staggering increase in the
proportion of the population over the age of 60 years. The increase in longevity
since the beginning of the twentieth century is approximately equal to that seen
in the human race in the previous 5000 years. We certainly need to know more
about the ageing process and its effects on the skin.
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Both the epidermis and the dermis become thinner on non-light-exposed sites
with the passing of the years. The degree of thinning is variable, but, between the
ages of 20 and 80, dermal thickness on the exor aspect of the forearm changes in
men from a mean of 1.1 mm to 0.8 mm. The epidermis thins from four to ve cells
thick at age 20 to approximately three cells thick at age 80. The individual keratinocytes also shrink with age, although the horn cells at the surface inexplicably
increase in area. Interestingly, the stratum corneum does not appear to change substantially in thickness during ageing.
Blood vessels decrease in number with age, but thicken. Adnexal structures also
decrease in size and number with increasing age. This applies also to the hair
(see page 268), but not always to the sebaceous glands, as on the face they may,
paradoxically, enlarge, which is sometimes clinically evident in the condition of
sebaceous gland hyperplasia (see page 188).
The dermal connective tissue loses much of its proteoglycan ground substance
and the collagen bres become mainly tough, insoluble and heavily cross-linked
biochemically. Pigment cells become fewer in number and smaller, and Langerhans
cells are also less in evidence in the skin of the elderly.
Functional changes
Wound healing is slower and may be less complete in the elderly. The aged
also respond less vigorously to chemical and physical trauma the erythema
and swelling are less marked and slower to develop. Delayed hypersensitivity is
depressed and this also applies to other components of the immune response.
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Old age
The activity of the pigment cells is depressed, and non-exposed areas of skin
are in general paler in the elderly than in young and mature subjects. On exposed
areas of skin, melanocytes show irregular increases in pigmentation.
Sweat gland responses to heating decrease, and the rate of sebum secretion also
decreases, although this is less marked than many other functions in the elderly.
Sensory discrimination decreases in the elderly, but, unfortunately, not the sensations of itch or pain!
As the skin ages, it becomes drier and tends to become itchier. This tendency is
heightened by:
The itchiness can be disabling and it is important to try to reduce the desiccating stimuli to which the skin is exposed. The generous use of emollients as topical applications as cleansing agents and of bath additives is mandatory.
Although itchiness due to dry skin in the elderly is quite common, it has to be
remembered that scabies and the other causes of generalized pruritus also occur
in this age group and should be diligently sought.
Eczema
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Treatment
The treatment of eczema in the elderly is similar to that in other age groups.
However, emollients are even more important and there should be greater readiness
to use systemic remedies, including cyclosporin, azathioprine and corticosteroids.
Case 14
William was 83 and lived by himself. His winter bronchitis worsened one day and
he developed pneumonia. After being in hospital for 4 days, his chest improved
with the use of antibiotics, but he began to develop an odd, itchy, crazy paving
pattern of rash on his shins. This eczema craquele was due to the increased
washing and decreased humidity in the hospital. It responded to reduced rubbing
and scrubbing and the use of emollients.
Skin tumours
Skin tumours are a frequent reason for the elderly consulting a physician.
Seborrhoeic warts are found in virtually everyone over the age of 60 years and,
although benign, often result in minor symptoms and some cosmetic embarrassment. They can easily be removed by curettage and cautery, but when present in
large numbers, can present an insoluble problem. Solar keratoses are another frequent cause of presentation some 4 per cent of all new patient consultations in
the dermatology department of the University Hospital of Wales were for solar keratoses. Although very few progress to squamous cell cancer, they indicate that serious solar damage has occurred and that more signicant lesions may develop. They
are uncommon below the age of 45 years and very common over the age of 60
years. As with seborrhoeic warts, solar keratoses may also cause minor symptoms
and some cosmetic problems.
Basal cell carcinomas (see page 214) are almost as common as solar keratoses.
Because of their capacity for local invasion and tissue destruction, they cause
considerable morbidity. Squamous cell carcinomas (see page 211) are much less
common, but can metastasize as well as cause local tissue destruction. Malignant
melanoma (see page 219) is slightly more common in the elderly compared to
young age groups, but lentigo maligna (see page 219) is virtually restricted to the
elderly.
Management of skin disorders in the elderly
Through no fault of their own, the elderly are often physically, socially and economically deprived. Their housing, hygiene, nutrition, clothing and means of
heating may all be decient, and this should be taken into account when designing treatments. If they live alone, as is often the case, they may well be unable to
nd anyone to help with the application of ointments to body parts they cannot
reach themselves or to assist with bandages because of lack of mobility.
It must be remembered that the elderly may also have difculty in hearing,
understanding and/or remembering instructions, especially if these are complex
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Summary
and involve more than one medicament. If possible, instructions on the medications should also be given to an accompanying relative or legibly written out.
The above potential difculties need to be taken into account when trying to
help an elderly patient with a skin problem.
Summary
Neonatal skin is not mature functionally, so that
excess water loss may occur, leading to dehydration.
Similarly, the barrier of infants skin is less efcient
than in adult life, permitting greater amounts of
topically applied agents to be absorbed. Infant skin
is also less able to withstand infection.
Rashes in the napkin area may be due to
erosive dermatitis on the convexities from
persistent skin contact with faeces and urine or
due to seborrhoeic dermatitis where the rash is
mainly in the exures. It may also be psoriasiform
in type, although the relationship of this to adult
psoriasis is uncertain. Frequent changes of nappies
and the use of softer materials, together with the
use of emollients and emollient cleaners and, if
required, hydrocortisone, will rapidly improve most
affected infants.
Atopic dermatitis starts at 24 months, with rash
on the face at rst. The ability to scratch does not
develop before 6 months of age, when the
distribution and appearance of the rash change.
Flexural lesions and excoriations start to develop.
Advice on bathing and the frequent use of
emollients and weak corticosteroids should help.
Infantile acne with seborrhoea, comedones, papules
and pustules is not uncommon and may be
persistent. If it develops late in infancy, look for
other signs of virilization (such as muscle growth).
The staphylococcal scalded skin syndrome occurs
in young infants and is a type of toxic epidermal
necrolysis. It is caused by the erythematogenic
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C H A P T E R
15
Pregnancy and
the skin
Physiological changes in the skin during pregnancy
238
240
240
241
Summary
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STRIAE GRAVIDARUM
Striae distensae (or stretch marks) are linear areas of apparent atrophy of the skin
due to disruption of dermal connective tissue bres (Fig. 15.2) as a result of ruptured dermal elastic bres. They occur at sites of skin stretching when there is
excess glucocorticoid activity. They occur normally in early adolescence, in
Cushings syndrome after both systemic and topical corticoid therapy, and in
pregnancy, when they are called striae gravidarum.
Striae gravidarum occur predominantly over the lower abdomen and over the
breasts during the third trimester and are of major cosmetic concern.
CUTANEOUS VASCULARITY
One of the oddest of phenomena that occur in pregnant women is the appearance
of small vascular malformations known as spider naevi (Fig. 15.3). These only
develop on the face, upper trunk and arms, i.e. the area of drainage of the superior vena cava. As with liver disease, in which these lesions also occur, it may be that
in pregnancy there is a relative excess of oestrogenic activity that provokes these
vascular anomalies. Also, the palms in pregnancy become redder and feel warmer,
as in liver disease. Both the spider naevi and the palmar changes fade following
delivery.
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PRURITUS IN PREGNANCY
Generalized itching is sometimes a problem for pregnant women. In some
instances, there appears to be intrahepatic cholestasis leading to biliary retention
in the last trimester. There is little that can be done concerning this problem, other
than using emollients and mentholated oily calamine preparations.
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INFECTIONS
These are of most concern now with regard to human immunodeciency virus
(HIV) infection, and frighteningly high rates of HIV positivity have been found
in pregnant women in some communities. Syphilis may still be a problem if undiagnosed and then transmitted congenitally. Other infective skin disorders that may
be passed from mother to fetus include chickenpox, herpes simplex, candidiasis
and warts, although the last two are better classied as intranatal infections, as
they are caught from the birth passages.
Case 15
Charlotte, aged 24, is 7 months pregnant with her rst child and has suddenly
developed an itching, red rash on her abdomen, buttocks and thighs. Apart from
striae and midline pigmentation, there are only a few nondescript papules to see.
This is the common maculopapular rash of pregnancy, which will quickly subside
when she has been delivered and will obtain some relief from simple emollients.
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Summary
The breast areolae, the midline of the abdomen, the
external genitalia and areas on the face become
hyperpigmented during pregnancy. The facial
changes, known as melasma, occur in 60 per cent
of pregnant women.
Striae distensae (or stretch marks) occur in
Cushings syndrome, during treatment with
corticosteroids, in pregnancy (striae gravidarum) and
in normal adolescence.
Spider naevi may develop during pregnancy.
Generalized itching may occur during the third
trimester due to intrahepatic cholestasis.
Inammatory dermatoses may either improve or
worsen during pregnancy. Great care should be
taken to ensure that the developing fetus is not
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Disorders of
keratinization and other
genodermatoses
C H A P T E R
16
Introduction
243
Xeroderma
245
246
Sex-linked ichthyosis
247
249
251
Lamellar ichthyosis
252
Collodion baby
252
254
Other genodermatoses
256
Summary
257
Introduction
EPIDERMAL DIFFERENTIATION
The differentiation process in which basal epidermal cells gradually mature and
transform into stratum corneum cells is known as keratinization. In this process,
which takes about 14 days, plump, cuboidal or spheroidal, hydrated, highly metabolically active cells gradually become tough, hardened, biochemically inactive,
thin, shield-like structures that are programmed to desquamate off the skin surface (Fig. 16.1). This process is biochemically complex and it is not surprising that
it is subject to genetically determined errors. During keratinization, a tough,
chemically resistant, cross-linked protein band is laid down just inside the plasma
membrane and the whole cell attens to a thin disc (corneocyte, Fig. 16.2). The
corneocytes water content is reduced from the usual 70 per cent to 30 per cent
and most of the cellular organelles, including its nucleus, are eliminated. The keratinous tonolaments become organized in bundles and are spatially orientated.
A further characteristic feature of the normal stratum corneum is the presence of
an intercellular cement material that contains non-polar lipid and glycoprotein.
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SCALING
A scale is merely an aggregate of horn cells that have failed to separate from each
other in desquamation, and the condition of hyperkeratosis is an exaggeration of
this problem. Thus, regardless of the particular metabolic fault ultimately responsible, the nal common pathogenetic pathway is a failure in the normal loss of
intercorneocyte binding forces (cohesion) in the supercial portion of the stratum corneum.
ICHTHYOSIS
The term ichthyosis (meaning sh) is unfortunate, as the scale of modern sh is,
in fact, mesodermal rather than ectodermal in origin. The term ichthyosis is used
to describe generalized, non-inammatory disorders of keratinization and
implies a congenital origin. However, there are many exceptions!
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Xeroderma
skin disorders often become severely depressed. Also, it is not often appreciated
just how severely physically disabled some patients with skin disease are. The
abnormal scaling and hyperkeratotic skin does not have the normally excellent
extensibility and compliance, so that movements are limited.
Xeroderma
Xeroderma does not represent a single disease process. The term derives from the
Greek xeros, meaning dry, and xeroderma just means dry skin. In fact, xeroderma
is used to describe scaliness rather than water content. Because the appearance of
scaling transiently disappears if the abnormal skin is hydrated, it has mistakenly
been believed that scaling is the manifestation of water deciency.
CAUSES
There are some normal individuals who tend to have a dry skin and they are
more susceptible to stimuli that provoke scaling of the skin surface. Ageing tends
to make the surface of the skin feel drier and this seems to be associated with pruritus in susceptible individuals. A low relative humidity aggravates the problem, as
does repeated vigorous washing, especially in hot water with some soaps and
cleansing agents. Presumably, the toilet procedures leach out important substances that are vital to the integrity of the stratum corneum. Xeroderma tends to
be worse in the wintertime and, when accompanied by itching, is known, logically
enough, as winter itch. This is particularly a problem in the north-eastern USA
because of the low relative humidity.
Xeroderma is seen in many patients with atopic dermatitis. It has been suggested that this is a manifestation of ichthyosis, but there is more evidence in
favour of the disorder being the result of the eczematous process itself. Xeroderma
is also seen during the course of severe wasting diseases such as carcinomatosis,
intestinal malabsorption and chronic renal failure, but should not be confused
with acquired ichthyosis (Table 16.1).
Table 16.1 Precipitating causes of acquired ichthyosis
Precipitating cause
Comment
Leprosy
AIDS
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KERATOSIS PILARIS
Horny plugs occur in the hair follicles of the outer aspect of the upper arms, forming sheets of pink, horny papules (Fig. 16.3), and occasionally on the thighs. It is
seen in ordinary xeroderma, in autosomal dominant ichthyosis, and sometimes
in normal young women for no apparent reason.
TREATMENT
Patients should be instructed to shower rather than bathe, to use lukewarm water
rather than hot water, to use emollient cleansing agents rather than ordinary
soaps, and to pat dry rather than vigorously towelling after bathing. If the patient
lives in centrally heated rooms, humidiers should be employed to raise the relative humidity. Emollients are a mainstay of treatment (see page 306). These act
by supplying an oily lm on the skin surface to prevent evaporation of water and
encourage a build-up of this in the skin. Emollients act for a short time only up
to 23 hours at most and need to be frequently applied. Their action can be
supplemented by bath oils, which deposit a lm of lipid on the skin surface.
CLINICAL FEATURES
There is widespread ne scaling over the skin surface, which tends to be worse in
the wintertime when the humidity is low. It spares the exures and is most noticeable over the extensor aspects of the limbs and trunk, being most noticeable over
the back, the lateral aspects of the upper arms, the anterolateral thighs and particularly the shins (Fig. 16.4). Keratosis pilaris may be seen over the outer aspects
of the upper arms in a few subjects. The condition is hardly noticeable in
most people, but is quite marked and disabling in a few. In the worst affected,
large, polygonal, dark scales form on the shins. The disorder is lifelong, but may
worsen in old age.
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Sex-linked ichthyosis
TREATMENT
Generally, little is required in the way of treatment other than emollients. Patients
who have very severe scaling may be helped by the use of topical keratolytic
agents, including preparations containing urea (1015 per cent) and salicylic acid
(16 per cent). The latter is particularly effective in encouraging desquamation,
but may not be used on large body areas for any length of time, as salicylic acid
preparations when applied to abnormal skin may cause salicylate intoxication (salicylism). Concentrations of more than 2 per cent may also irritate the skin.
Sex-linked ichthyosis
DEFINITION
This is an uncommon, moderately severe disorder of keratinization that is inherited
as a sex-linked characteristic in which the underlying metabolic fault is deciency
of steroid sulphatase.
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CLINICAL FEATURES
The male children who are born with this disorder are often the products of postmature pregnancies and difcult labours. The reason for this appears to be a placental deciency of the steroid sulphatase and a consequent failure of the usual
splitting of circulating maternal oestrone sulphate in the last trimester of pregnancy.
The free oestrone is thought to have a role in priming the uterus to oxytoxic stimuli.
The scaling is usually more severe than in autosomal dominant ichthyosis
(Fig. 16.6). It is also more marked over the extensor aspects of the body surface,
but does not always spare the exures and often affects the sides of the neck and even
the face. The scales are often quite large, particularly over the shins and have a
dark-brownish discoloration. Patients with sex-linked ichthyosis may be signicantly disabled by their disorder.
ASSOCIATED DISORDERS
There is an association with cryptorchidism and, rarely, even with testicular cancer
on the basis of this. There is also an association with a form of cataract.
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the carrier female may demonstrate patchy scaling that is consistent with the random deletion (or Lyon) hypothesis. The disorder is quite uncommon, having a
gene frequency of approximately 1 in 6000.
Histologically, there is a minor degree of epidermal thickening and mild hypergranulosis. Biochemically, affected male subjects show a steroid sulphatase deciency, but for diagnostic purposes, broblast, lymphocyte or epidermal cell
cultures are tested. The steroid sulphatase abnormality results in excess quantities
of cholesterol sulphate in the stratum corneum with diminished free cholesterol.
This has been used as the basis of a diagnostic test and has been suggested as the
underlying basis for the abnormal scaling.
TREATMENT
Treatment is as for autosomal dominant ichthyosis, but some patients may need
oral retinoids.
Case 16
J.S. presented at the age of 17 with generalized scaling, dry skin. He had had
it since birth, although it didnt start to be a problem until he reached the age of
11. He complained of itchiness especially in the wintertime, when, in addition
to the itch, the skin of his hands became sore and cracked in places. He had
a brother who was affected and his maternal grandfather also had the disease.
Close questioning of his mother revealed that J.S. was born 2 weeks late after
a difcult delivery. It was clear that he had sex-linked ichthyosis, which could
be expected to persist, but the symptoms of which should be helped by
emollients.
CLINICAL FEATURES
Characteristically, there is generalized erythema and ne scaling (Fig. 16.7). There
is a history of a collodion membrane (see page 252) in a few patients. Ectropion,
deformities of the ears and sparsity of scalp hair are common accompaniments.
Neurological and immunological abnormalities occur in some patients. The condition persists throughout life, although the erythema tends to decrease.
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TREATMENT
Topical treatments with emollients and keratolytics as for patients with autosomal
dominant ichthyosis may be sufcient.
Severely affected patients may benet from the use of long-term oral retinoid
drugs. The agent usually used is acitretin, but isotretinoin has been used for some
patients. The dose of these drugs is 0.30.7 mg/kg body weight per day, given in
two divided doses daily with food. The disorder starts to improve after 24 weeks,
but full improvement may not take place before 6 weeks.
The oral retinoids appear to affect the process of keratinization rather than any
particular component of NBIE. Although there is often considerable improvement, evidence of the underlying problem is always present, and the condition
always relapses when treatment is stopped. The oral retinoids have major and
minor toxicities (see page 140) and are markedly teratogenic, so that fertile
women must use effective contraception. Patients must be regularly monitored
for hepatotoxicity, hyperlipidaemia and bone toxicity. Most patients notice drying
of the mucosae of the lips particularly and some an increase in the rate of
hair loss.
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Figure 16.8 Epidermolytic hyperkeratosis showing typical severe hyperkeratosis and scaling.
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carefully regulated, as these drugs may temporarily increase the blistering as well
as decreasing the hyperkeratosis!
Lamellar ichthyosis
This is a rare, autosomal recessive disorder of keratinization, characterized by a
striking degree of hyperkeratosis but not much erythema. As with NBIE and epidermolytic hyerkeratosis, some patients develop the condition after being born in
a collodion membrane. The hyperkeratosis may be discoloured brown, for reasons
that are unclear (Fig. 16.11). As with the other severe disorders of keratinization,
there may be marked ectropion and ear deformities (Fig. 16.12).
Histologically, there is marked hyperkeratosis and hypergranulosis.
Treatment is similar to that for NBIE and epidermolytic hyperkeratosis, with
oral retinoid drugs being the only available agents that can produce any substantial improvement.
Collodion baby
This is an odd condition in which babies are born covered by a shiny, transparent
membrane (Fig. 16.13). This gradually peels off after a week or so, the peel looking
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Collodion baby
like collodion hence the name. Ultimately, the child may develop normally or
may develop one of the severe disorders of keratinization discussed above.
Nothing is known of the cause. Collodion babies need to be carefully nursed,
as their skin barrier function may be abnormal, so that they lose much water and
become dehydrated.
HARLEQUIN FETUS
This is a rare and mostly fatal disorder in which the child is born encased in thick,
abnormal, ssured, hyperkeratotic skin. This disorder is also due to abnormalities
of keratin synthesis. Survival of a few of these unfortunate children has been
reported with the use of oral retinoids.
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ACQUIRED ICHTHYOSIS
Generalized skin scaling without accompanying inammation develops in adult
life in this disorder. The most important cause of acquired ichthyosis is underlying malignant disease particularly lymphoma such as Hodgkins disease (see
Table 16.1).
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TYLOSIS
This term describes a group of disorders in which there is marked thickening
of palmar and plantar skin due to some localized abnormality of keratinization
(Fig. 16.16). The disorder is clearly heterogeneous, with autosomal dominant,
autosomal recessive and sex-linked recessive types being described. There is also a
wide range of clinical features, with involvement of the dorsa of the hands and feet
in some patients and an odd punctate palmar pattern in others.
In one inherited variety, there is a close association with the development of
carcinoma of the oesophagus.
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Fortunately, most patients are not as disabled as may be thought from the clinical appearance. As long as they keep their skin surface exible and smooth with
emollients and keratolytics, they can manage everyday activities quite well.
PACHYONYCHIA CONGENITAL
This is a rare, autosomal recessively inherited disorder in which there is striking
thickening of the nails. There are also hyperkeratotic areas over the palms and
sometimes elsewhere.
Other genodermatoses
TUBEROUS SCLEROSIS
Tuberous sclerosis is a rare, autosomal dominantly inherited disorder in which
defects occur in many organ systems.
Major skin abnormalities include the appearance of pink-red papules around
the nose and cheeks, which increase in number during adolescence and are
known, inappropriately, as adenoma sebaceum. Firm, whitish plaques (shagreen
patches) with a cobblestone surface, depigmented leaf-shaped macules and subungual bromata are other skin signs. Cerebral malformations often result in
epilepsy. Renal hamartomas occur in 50 per cent of patients. Mental deciency is
seen in many patients with this disease.
Brown macules appear, varying in size and aptly described as caf au lait
patches, characterized by the presence of giant melanosomes. The appearance
of such freckle-like lesions in the axillae is diagnostic of the disorder.
Skin-coloured to pink-mauve compressible, soft skin tumours develop, some
of which are pedunculated (Fig. 16.17). These are neurobromata and may be
present in large numbers, causing a considerable cosmetic disability.
Larger tumours of the limbs occur. These are plexiform neuromas.
The numbers of lesions increase with age. Patients are also subject to the development of a wide range of neoplastic lesions, including acoustic neuroma,
phaeochromocytoma and brosarcoma.
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Summary
Summary
Keratinization involves the transformation of
epidermal cells into tough, thin, shield-like
corneocytes, which make up the stratum corneum
barrier.
Scaling is the result of failure of the nal stage of
keratinization in which corneocytes separate
individually. Thus, a scale is an aggregate of
unseparated corneocytes and occurs in any
disturbance of keratinization congenital or
acquired.
Scaling may cause considerable disability, both
physical and psychological. Xeroderma just means
dry skin which is, in fact, scaling skin and due to
a wide variety of disturbances of keratinization.
Xeroderma is common in the elderly and in atopic
eczema and is worse in low relative humidity such
as in wintertime.
Treatment of xeroderma is focused on the frequent
use of emollients and emollient cleansers as well
as on gentle showering rather than bathing.
Autosomal dominant ichthyosis is characterized by
generalized ne scaling that is worse on the
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Metabolic disorders
and reticulohistiocytic
proliferative disorders
C H A P T E R
17
Porphyrias
259
Necrobiotic disorders
265
266
Summary
267
Porphyrias
The porphyrias are a group of disorders of metabolism of the haem molecule.
Acute, intermittent porphyria has no skin manifestations. Porphyrias that demonstrate skin disorder as a component are summarized in Table 17.1.
There appears to be a defect in the action of the enzyme uroporphyrinogen decarboxylase, resulting in the accumulation of uroporphyrins and coproporphyrins in
the blood, stools and urine.
Clinical features
When associated with alcoholic liver disease, the disorder is more often seen in
middle-aged men. The characteristic features are seen in the light-exposed areas.
In the early stages of the disease, blistering and fragility of the skin on the face and
backs of the hands are noted (Fig. 17.1). The affected areas also develop an odd
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Enzyme affected
Inheritance
Uroporphyrinogen
decarboxylase
Autosomal dominant/
acquired
Variegate porphyria
Protoporphyrinogen
oxidase
Autosomal dominant
Erythropoietic porphyria
(Gunthers disease)
Uroporphyrinogen
cosynthetase
Autosomal recessive
Erythropoietic protoporphyria
Ferrochelatase
Autosomal dominant
pigmented and mauve, suffused appearance (Fig. 17.2). Later, increased hair growth
occurs on the involved skin and a sclerodermiform thickening of the skin develops.
The diagnosis is made by nding increased uroporphyrins and coproporphyrins
in the stools and urine. If available, monochromatic testing (to irradiate the skin
with very narrow wavelength bands of light or ultraviolet radiation) will reveal
photosensitivity at 404 nm.
Pathology and pathogenesis
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Porphyrias
PORPHYRIA VARIEGATA
This is a very rare combination of PCT and acute intermittent porphyria. The
latter is caused by a deciency of delta-aminolaevulinic acid synthetase and is precipitated by certain drugs and anaesthesia, amongst other things.
ERYTHROPOIETIC PROTOPORPHYRIA
Erythropoietic protoporphyria is a very rare, autosomal dominant disorder in
which excess protoporphyrins are produced. These protoporphyrins are detectable
in the blood and this forms the basis of diagnostic tests. Clinically, the disorder
often presents in childhood as episodes of skin soreness and extreme discomfort
when exposed to the sun. Swelling, redness and urticarial lesions may develop
in exposed skin. Later, ne, pitted scarring is found on exposed sites. Pigment
gallstones may develop.
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AMYLOIDOSIS
Amyloidosis is the term used for a group of disorders in which an abnormal protein is deposited in tissues. Generalized amyloidosis is divided into primary and
secondary forms. The latter develops after long-standing inammatory disease,
including infections such as chronic tuberculosis and chronic osteomyelitis. It may
also occur in patients with long-standing severe rheumatoid arthritis. There are no
skin manifestations in secondary amyloidosis. In primary amyloidosis, the abnormal protein components are synthesized by clones of abnormal plasma cells and
the condition is sometimes associated with multiple myeloma. In primary amyloid
disease amyloid is deposited in various organs as well as in the skin. In the skin,
it is deposited in and around the dermal capillary blood vessels, which become
fragile and leaky. Swollen mauve-purple areas develop around the eyes and around
the exures.
There are also amyloid disorders that are restricted to the skin. In the rare macular amyloid, itchy, rippled, brown macular areas appear over the trunk (Fig. 17.3).
It seems to be more common in women and in patients of Asian origin. Histologically, the deposits of amyloid are detectable subepidermally. Lichen amyloidosis
is another rare cutaneous form of amyloid in which lichen planus-like lesions
occur.
Amyloid can be detected in tissue using various histochemical tests, including
birefringence with Congo red stain and uorescence with thioavine T, as well as
by immunocytochemical tests.
XANTHOMATA
Xanthomata are deposits of lipid in histiocytes in skin and may be associated
with normal levels of lipids in the blood (normolipaemia) or with elevated
levels of serum lipids (hyperlipidaemia). The lipidized histiocytes have a characteristic foamy appearance. The main hyperlipidaemic conditions are given in
Table 17.2.
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Porphyrias
Plasma
cholesterol
Plasma
triglycerides
Lipoproteins
elevated
Inheritance
Skin lesions
Systemic
manifestations
Chylomicrons
Autosomal
recessive
(BurgerGrtz
disease
Eruptive
xanthomata
Pancreatitis
Hepatosplenomegaly
Lipaemic retinalis
II
LDL
LDL, VLDL
Autosomal
dominant (familial
hypercholesteraemia)
Xanthelasma
Tendon/
tuberous
xanthoma
Corneal arcus
Accelerated
atherosclerosis
III
Chylomicron
Remnants LDL
Uncertain
Planar
xanthoma
Eruptive and
tendon
xanthoma
Accelerated
atherosclerosis
IV
VLDL
Uncertain
Eruptive
xanthoma
Accelerated
atherosclerosis
Glucose intolerance
Hyeruricaemia
VLDL
Chylomicrons
Uncertain
Eruptive
xanthoma
Pancreatis
Hepatosplenomegaly
Sensory neuropathy
Lipaemia retinalis
Hyperuricaemia
Glucose intolerance
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Xanthelasma
The lesions of xanthoma tuberosum are large nodules containing lipidized histiocytes and giant cells. The nodules develop around the tendons and extensor
aspects of the joints in familial hyperlipidaemia (see Table 17.2), particularly over
the Achilles tendon, the knees and elbows (Fig. 17.5).
Eruptive xanthomata
These mostly develop in diabetes, but are also seen in congenital deciencies
of lipoprotein lipase (BurgerGrtz disease: see Table 17.2). Large numbers of
yellowish-pink papules develop rapidly over the skin surface (Fig. 17.6).
Treatment
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Necrobiotic disorders
Necrobiotic disorders
The term necrobiosis is applied to a particular histological change in which there
are foci of damage making the dermal structure blurred and more eosinophilic
than usual. The foci are surrounded by inammatory cells lymphocytes, histiocytes and occasional giant cells (Fig. 17.7)
GRANULOMA ANNULARE
This, not uncommon, inammatory disorder, often seen in children and young
adults, is characterized by papules and plaques that adopt a ring-like pattern
(Fig. 17.8). Lesions develop on the extensor aspects of the ngers, dorsa of the
feet, hands and wrists.
Granuloma annulare tends to last for a few months and then disappears as
mysteriously as it came. Treatment is generally not indicated.
A less common type, known as generalized supercial granuloma annulare,
is characterized by macular, dull-red or mauve areas rather than rings (Fig. 17.9),
which have a necrobiotic structure histologically. Diabetes is more common in
this group of patients.
Case 17
Annie, aged 11, was brought to the surgery because of several pink plaques that had
developed in the previous 3 months on her ankles and the backs of the hands. The
plaques were static and did not trouble her. They were clinically typical of granuloma
annulare and this was conrmed by the nding of necrobiotic and granulomatous foci
histologically. They resolved without treatment after a further 6 months.
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Summary
Summary
The porphyrias are disorders of haem molecule
metabolism. In porphyria cutanea tarda, there is a
defect in uroporphyrinogen decarboxylase, causing
uroporphyrins and copirorphyrins to accumulate in
the blood, stools and urine. PCT is associated
with liver disease; its genetic basis is uncertain.
Mauvish discoloration, blistering and hirsutes
occur in light-exposed sites.
Treatment is by regular venesection or by
administration of chloroquine, both of which
reduce levels of abnormal circulating porphyrins.
Porphyria variegata is a very rare, dominant
combination of PCT and acute intermittent
porphyria. Erythropoietic protoporphyria is another
rare, dominantly inherited disorder with
photosensitivity.
In primary haemochromatosis, there is excessive
gastrointestinal absorption of iron, with its
subsequent deposition in the viscera particularly
in the skin, causing pigmentation, and in the liver
and pancreas, causing cirrhosis and diabetes,
respectively. Secondary haemochromatosis occurs
as a result of chronic haemolysis or repeated
blood transfusion.
Amyloidosis describes a group of disorders in
which there is deposition of an abnormal protein.
Primary generalized amyloidosis is the result of an
abnormal clone of plasma cells and results in
amyloid deposition perivascularly in skin and
various organs. Secondary amyloidosis from
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C H A P T E R
18
Disorders of hair
and nails
Disorders of hair
268
276
Summary
279
Both hair and nails are epidermal structures that arise from invaginations of the
epidermis into the skin (Figs 18.1 and 18.2). Hair and nails may develop signs of
disorder such as psoriasis or lichen planus in the absence of obvious skin disease.
In addition, there are disorders that are conned to either the hair or the nails.
Disorders of hair
(Table 18.1)
Denition
This is a common, dominantly inherited, progressive form of alopecia, which is
mostly seen in men, develops symmetrically at certain specic sites on the scalp
and eventually causes almost complete scalp hair loss in some patients.
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Disorders of hair
Epidermis
Sebaceous gland
Hair matrix
Hair papilla
(a)
(b)
(c)
Figure 18.1 (a) Diagram of a hair follicle showing the relationship between the hair
shaft, follicular epithelium and sebaceous glands. (b) Photomicrograph to show a hair
follicle on the scalp with arrectores pilorum muscles. (c) Photomicrograph to show a
hair follicle on the scalp with prominent hair matrix and hair papillae.
Nail plate
Nail matrix
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Hair loss
(alopecia)
Non-scarring
Scarring
Diffuse
Ageing
Telogen efuvium
Drug induced
Localized
Trauma
Lupus erythematosus
Lichen planus
Constitutional
Androgenization
Drug induced
Clinical features
Loss of hair starts in both temporal regions. Shortly after this bitemporal recession,
thinning of the hair and then alopecia develop over the vertex. The bald area over the
vertex expands to meet the triangular temporal bald areas until, in the worst cases,
almost complete loss of hair results. A general reduction in the density of hair follicles
also occurs and this may be the main feature of the disorder in women, in whom
bitemporal recession and some vertical thinning occur less commonly than in men.
The condition may start as early as in the late teens, but generally declares its
presence in the third decade. Its rate of progress varies and seems uninuenced by
environmental factors.
Pattern alopecia causes an enormous amount of psychological distress and
patients will go to extraordinary lengths to attempt to arrest and reverse the
process and/or to disguise its presence. The condition is rmly embedded in popular mythology with regard to its supposed causes, which range from dietary
deciencies to sexual excesses.
Pathology and pathogenesis
The hair follicles in the affected areas become smaller and sparser and eventually
disappear. Finally, true atrophy of the skin occurs at the involved sites. The disorder is dominantly inherited, but requires androgenic stimulus in the form of
testosterone and the passing of the years for full phenotypic expression. The disorder can be precipitated by the administering of testosterone to female patients and
is also a sign of masculinization in patients with a testosterone-secreting tumour.
Treatment
There is no effective treatment. The progress of pattern alopecia in men may be
halted by castration, but there are few patients who would undergo the operation
for this purpose. In women, chemical castration with the use of an antiandrogenprostagen combination (cyproterone acetate and ethinylestranol
Dianette) has been tried and some reduction in the rate of hair loss claimed. The
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Disorders of hair
wigs and toupes and hair weaving, in which the remaining hair is woven to
cover the defect
surgical manoeuvres, in which plugs of hair-containing skin from the scalp
periphery are transplanted to holes made in the bald area or aps of skin are
advanced over bald areas.
Alopecia areata
Denition
Alopecia areata is an autoimmune disorder of hair follicles causing loss of hair in
sharply dened areas of skin.
Clinical features
Alopecia areata often starts quite suddenly as one or more rounded patches from
which the hair is lost (Fig. 18.3). The hair loss continues for days or weeks, until
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all the hair from the affected sites has fallen. The individual areas vary in size from
1 cm2 to involvement of the entire scalp (alopecia totalis); rarely, the eyelashes and
eyebrows (Fig. 18.4) and all body hair are lost as well.
Affected areas may extend outwards and disease activity can be recognized by
the appearance of so-called exclamation mark hairs at the margin of the lesions.
The condition occurs over a wide age range, but seems particularly common
between the ages of 15 and 30 years.
Regrowth of alopecia areata patches occur in most patients if the affected areas
are small, limited in number, and the affected individual is 15 years old or less.
When regrowth occurs, the new hair is ne and non-pigmented (Fig. 18.5). The
outlook for regrowth worsens when large areas are affected, the patient is over
30 years old and also has atopic dermatitis.
Pathology and pathogenesis
The disorder is positively associated with autoimmune disorders, including
vitiligo and thyrotoxicosis, and it has been assumed that an immune attack is
launched against components of the hair follicle. When biopsies are taken from an
actively extending patch, a dense bee swarm-like cluster of lymphocytes can be
seen around the follicles.
Differential diagnosis
Patches of baldness due to hair pulling (trichotillomania) are bizarrely shaped,
not as well demarcated as alopecia areata, and have no exclamation mark hairs at
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Disorders of hair
the edge. Tinea capitis is marked by broken hairs and by a degree of redness and
scaling of the scalp skin. Disorders that iname the skin and destroy hair follicles
can usually be easily differentiated by the scarring they cause.
Treatment
Patients with a solitary patch or few patches usually do not need treatment. When
the patches coalesce to become a problem cosmetically or when there is alopecia
totalis, treatment is often demanded by patients, but is not often effective. The following treatments have been used: potent topical steroids or systemic steroids;
photochemotherapy with long-wave ultraviolet irradiation (PUVA); dithranol;
allergic sensitization with diphencyprone; and topical minoxidil has been claimed
to be partially successful. All of the above have inconvenient side effects and usually work only while they are being given.
Allergic sensitization with 1 per cent diphencyprone causes an eczematous
response and kicks the follicles back to life in about half the patients and is quite
often used.
Many patients, having experienced the side effects and frustration of the lack
of efcacy of the treatments, decide to cut their losses and disguise their disability with a wig. Sympathy and support are the most useful applications for this
depressing disorder.
Diffuse hair loss
The human hair cycle (Fig. 18.6) is asynchronous, but can be precipitated into
synchrony by childbirth or a sudden severe systemic illness such as pneumonia or
massive blood loss. The stimulus causes all the scalp hair follicles to revert to the
telogen, or resting, phase. There is a sudden and signicant loss of terminal scalp
hair some 3 months after the precipitating event, which continues for a few weeks
but then spontaneously stops. Hair regrowth gradually restores the scalp hair to
its original state.
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Anagen
Catagen
Telogen
Remnant of i
root sheath
Sebaceo
duct
Outer root
sheath
Inner root
sheath
Early anagen
Outer root
sheath
Inner root
sheath
ub
Club
Sebaceous
gland
Telogen
lub hair
b
agen hair
Dermal papilla
Basal lamina
Dermal papilla
Dermal papilla
Dermal papilla
Figure 18.6 Diagram showing the various stages of the human hair cycle.
Traction alopecia
Repeated tugging and pulling on the hair shaft may produce loss of hair in the
affected areas, such as occurs when hair rollers are used (Fig. 18.7). It can also develop
in young children when they continually rub their scalp on their pillow. Youngsters
sometimes tug at their hair, producing the same effect in a bizarre distribution over
the scalp (trichitillomania, Fig. 18.8). The motivation for this strange behaviour usually remains obscure. The main differential diagnosis is alopecia areata.
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Disorders of hair
Scarring alopecia
Any inammatory process on the scalp sufcient to cause loss of follicles and scar
formation will result in permanent loss of hair in the affected area. Mechanical
trauma, burns, bacterial infections and severe inammatory ringworm of the
scalp can produce sufcient damage to cause scarring and permanent hair loss.
In discoid lupus erythematosus (see page 79) and lichen planus (see page 144),
the scalp skin may be characteristically affected by the dermatosis concerned, but
it may be difcult to distinguish these two conditions, even after biopsy. Usually,
the affected area is scarred and there is loss of follicular orices the few remaining being distorted and dilated and containing tufts of hair (Fig. 18.9). An odd and
unexplained type of scalp scarring known as pseudopelade is characterized by
small, rounded patches of scarring alopecia without any inammation.
Hair shaft disorders
Hair shaft abnormalities may be either congenital or acquired. Acquired abnormalities are more often seen. All long hairs tend to become weathered at their
ends due to climatic exposure and the usual washing and combing routines.
Twisting hairs between the ngers, and other obsessive manipulation of hair,
results in a specic type of damage to the hair shafts known as trichorrhexis
nodosa, in which expansions of the shaft (nodes) can be seen by routine light
microscopy and scanning electron microscopy. These nodes rupture and leave
frayed, paintbrush-like ends (Fig. 18.10). This deformity leads to broken hairs
and even to the complaint of loss of hair.
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HIRSUTES
This is the name given to the complaint of excessive hair growth in women. When
the hair growth is on the chin and upper lip, it causes considerable cosmetic
embarrassment, even though in most cases it is normal. When hair growth is
marked on the trunk and limbs, is accompanied by acne, early pattern alopecia
and menstrual irregularities, tests for masculinization and polycystic ovarian syndrome should be performed. Removal of facial hair is usually by depilatories, waxing or electrolysis.
Psoriasis, lichen planus and eczema may all affect the nails, causing characteristic
clinical appearances. Psoriasis characteristically causes thimble pitting of the ngernails (Fig. 18.12). It also causes well-dened pink/brown areas and onycholysis
(separation of the nail plate from the nail bed: Fig. 18.13). The toenails rarely
show these changes, but the nail plates may be thickened, with a yellowish brown
discoloration and subungual debris often making it difcult to distinguish from
ringworm of the nails. In lichen planus, the nail plate may develop longitudinal
ridging (Fig. 18.14), which, in the worst cases, may penetrate the whole nail.
The process may even destroy the nail matrix and cause permanent loss of the
nail. Eczema affecting the ngers may cause irregular deformities of the ngernails and even marked horizontal ridging.
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PARONYCHIA
This term is applied to inammation of the tissues at the sides of the nail. In the
common form of chronic paronychia, the paronychial skin is thickened and reddened. It is often tender, and pus may be expressed from the space between the
nail fold and the nail plate. The eponychium disappears and the nail plate is often
discoloured and deformed (Fig. 18.15) and may demonstrate onycholysis (see
below). There is a deep recess between the nail fold and the nail plate, containing
debris and micro-organisms, which it is difcult to keep dry. The condition
mostly occurs in women whose occupation involves frequent hand washing or
other wet activities (e.g. cooks, cleaners, barmaids), and it seems likely that the
inability of this group of individuals to keep their hands dry contributes substantially to the conditions chronicity.
Candida micro-organisms may contribute to the recurrent inammation to
which the affected ngers are subject, but they are not the cause of the disorder.
The cause is compounded from mechanical trauma and over-hydration resulting
in microbial overgrowth in the nooks and crannies of the nail fold.
Treatment
The major goals in management are keeping the ngers completely dry and the
avoidance of manual work. Antimicrobial preparations in aqueous or alcoholic
vehicles are also useful (e.g. povidone-iodine or an imidazole lotion). Acute exacerbations may need to be treated with systemic antibiotics.
Providing the advice is taken and the treatment used, patients usually gradually improve.
ONYCHOLYSIS
Onycholysis is a physical sign in which the terminal nail plate separates from the
underlying nail bed. It is observed in psoriasis, eczema, chronic paronychia, the
yellow nail syndrome (see below), thyrotoxicosis, as a result of repeated mechanical trauma and for no known reason.
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Case 19
Pauline, aged 30, worked in a mobile phone factory and noticed that she was
nding it difcult to pick up small articles from the bench because her nails
showed some separation from the nailbeds. The dermatologist told her that this
was called onycholysis and was due to her psoriasis.
BROWN-BLACK PIGMENTATION
Pigmented linear bands along the length of the nail may be due to a mole or, if of
recent onset, may be caused by a malignant melanoma. Brown-black areas may be
due to melanin or haemosiderin from trauma, and the two may be very difcult
to tell apart (Fig. 18.16). Uncommonly, Pseudomonas infection of the nail plate
produces a diffuse black or black-green pigmentation. A blackish, yellow-green
discoloration is also seen in the yellow nail syndrome (Fig. 18.17). In this rare disease, nail growth is greatly slowed and the nails are yellowish green, thickened and
show increased curvature. In addition, ankle and facial oedema, sinusitis and
pleural effusion often accompany this condition, which is of unknown cause.
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Summary
(b)
(a)
Figure 18.18 (a) Deformity, discoloration and subungual debris in a big toenail due to ringworm infection (tinea
unguium). (b) Here, the second toe is also affected.
Summary
Hair loss may be non-scarring or scarring. Pattern
alopecia is a common, dominantly inherited,
progressive, non-scarring alopecia. Starting in the
temporal regions and on the vertex, it gradually
spreads, even involving the entire scalp. The
follicles become smaller in the affected area and
then disappear. Although it is heritable, the
androgenic stimulus of testosterone is needed for
expression of the disorder. There is no effective
treatment for men other than surgical transplant
techniques. In women, the anti-androgen
cyproterone acetate with ethinyl oestranol (Dianette)
has been used, as has the 5-alpha-reductase
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C H A P T E R
19
Systemic disease
and the skin
Skin markers of malignant disease
281
285
288
Androgenization (virilization)
289
291
292
Hepatic disease
292
293
Summary
293
This is usually caused by a tumour of the pancreatic islet alpha cells that secrete
glucagon, but it is sometimes caused by hyperplasia or benign adenomatosis of
these cells. Rarely, no underlying abnormality can be found. Areas of erythema,
which become eroded and crusted (Fig. 19.1), develop around the groins, on the
lower trunk, around the exures and at the sides of the mouth. They may temporarily remit at one site, to appear elsewhere. The skin disorder responds to
removal of the underlying tumour, but usually complete removal is not possible.
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Comment
Acquired ichthyosis
Acanthosis nigricans
Dermatomyositis
Erythema gyratum repens Very rare; strong association with underlying carcinoma
Necrolytic migratory
erythema
Bullous pemphigoid
Skin metastases
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Acanthosis nigricans
Acanthosis nigricans may occur in association with endocrine disease and also,
rarely, accompanies lipodystrophies. An identical clinical picture accompanies obesity and is then known as pseudoacanthosis nigricans. When the condition occurs in
an adult unaccompanied by obesity or endocrine disease, an underlying neoplasm is
usually the cause. The neoplasm involved is often a gastrointestinal adenocarcinoma.
There is a velvety thickening and increased rugosity of the skin of the exures
the axillae and groins in particular (Fig. 19.3). The sides and back of the neck and
the sides of the mouth are also affected.
The thickened areas are also pigmented and bear skin tags and seborrhoeic warts
(Fig. 19.4). There may also be some generalized increase in pigmentation, as well as
thickening and increased rugosity of the buccal mucosa and the palmar skin.
There is overall hypertrophy of all components of the skin of the affected areas.
Insulin-like growth factors may be involved.
Erythema gyratum repens
This is probably the rarest of the specic skin markers of visceral malignancy. This
odd disorder is almost always a marker of a neoplasm, often carcinoma of the
bronchus.
Large rings composed of reddened polycyclic bands are seen; the rings contain
concentric rings, giving a wood-grain effect (Fig. 19.5). The rings gradually
enlarge and change shape. Rarely, other less dramatic types of annular erythema
may be signs of an internal malignancy.
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Skin metastases
Carcinomas of the breast, bronchus, stomach, kidney and prostate are the most
common visceral neoplasms to metastasize to the skin. Secondary deposits on the
skin may be the rst sign of the underlying visceral cancer. The lesions themselves
are usually smooth nodules, which are pink or skin coloured (Fig. 19.6), but may
be pigmented in deposits of melanoma.
Acquired ichthyosis
When generalized scaling without erythema begins in adult life, it is quite likely
that there is an underlying neoplasm, particularly a reticulosis. This has to be distinguished from mild dryness of the skin and the slight irritation seen in many
chronic disorders, known as xeroderma.
Other causes of acquired ichthyosis include acquired immune deciency syndrome (AIDS), sarcoidosis and leprosy, but if these can be excluded, a neoplastic
cause is the most likely explanation (Fig. 19.7).
This subepidermal blistering disorder occurs mainly in those over 60 years of age,
who are anyway more likely to be affected by a neoplasm. Nonetheless, there are a
few patients with pemphigoid in whom the skin disorder is provoked by the
malignancy and remits after the neoplasm has been removed.
Dermatomyositis
Women over the age of 40 years with dermatomyositis may have 50 per cent
chance of a malignant tumour of the genitourinary tract, but infants with the
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disease have no greater risk than a control group. Overall, even in adults, the association is not common and most cases of dermatomyositis occur without an identiable cause. There is an impression that dermatomyositis provoked by malignant
disease is more severe.
Figurate erythemas
Rarely, annular erythema and erythema multiforme (see page 75) seem to be
caused by underlying malignant disease.
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be coarsening of the scalp hair, hair loss, loss of the outer third of the eyebrows,
pinkish cheeks but a yellowish background colour the so-called peaches and
cream complexion.
The skin manifestations of diabetes are summarized in Table 19.2. The most specic is necrobiosis lipoidica. More than 50 per cent of individuals who present
with this disorder will already have insulin-dependent diabetes. Many of those
who do not have diabetes when they present will develop diabetes or have a rstdegree relative with diabetes.
Typically, irregular yellowish pink plaques occur on the lower legs and around
the ankles (Fig. 19.9). Uncommonly, lesions may occur elsewhere and there may be
areas of atrophy and ulceration. These plaques are persistent and quite resistant to
treatment.
Histologically, there is a central area of altered and damaged collagen in the
mid-dermis, surrounded by inammatory cells, including giant cells.
Case 20
Julie, aged 19, reported to her GP that she was micturating much more often than
usual and was also feeling abnormally thirsty. When she was examined, the
doctor found an elevated, irregular, yellowish pink patch measuring 2.5 by 4.0 cm
on her left shin. There was also a smaller, similar patch on her right lower leg.
These patches had been present for 6 months. They had originally enlarged in
size, but were now static. It was thought that Julie had diabetes and that the leg
patches were due to necrobiosis lipoidica diabeticorum. It was explained to her
that, unfortunately, there was no certain cure for the disorder.
Comment
Necrobiosis lipoidica
Xanthomas
Neuropathic ulceration
Ischaemic changes
and infection
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Granuloma annulare
This disorder has some supercial resemblance to necrobiosis lipoidica, both clinically and histologically, but in its common form has no association with diabetes.
However, there is a rare, generalized and diffuse form that is strongly related to
diabetes.
Ulceration of the skin in diabetes
Xanthomata are due to deposits of lipid within dermal histiocytes. Their clinical
appearance and lipid composition depend on the type of lipid abnormality.
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CUSHINGS SYNDROME
The cutaneous signs of Cushings syndrome are the same regardless of whether
they are caused by an adrenal tumour, hyperplasia or the administration of
corticoids.
Clinical features
The most consistent clinical feature is skin thinning. The underlying veins can
be easily seen and the skin has a transparent quality (Fig. 19.12). The thinning
is due to the suppressive action of glucocorticoids on the growth and synthetic
activity of dermal broblasts and the epidermis.
The dermal thinning also results in rupture of the elastic bres and striae distensae (Fig. 19.13). These are band-like atrophic areas that develop in areas of
maximal stress on the skin. A certain number are found on the upper arm, the
anterior axillary fold, the lower back and occasionally elsewhere in normal
adolescents. They also occur in most pregnant women on the thighs, breasts,
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Androgenization (virilization)
anterior axillary folds and lower abdomen. It is thought that both tissue tension and the level of circulating glucocorticoids are important in the production of striae.
Acne papules occur on the chest, back and face in most patients with Cushings
syndrome. Steroid acne lesions are more uniform in appearance than adolescent acne and consist predominantly of small papules with few comedones.
This type of acne is more resistant to treatment than ordinary acne.
Skin infections are also more common and more severe in patients with Cushings
syndrome. Pityriasis versicolor is often present and often very extensive.
ADDISONS DISEASE
This disorder, due to destruction of the adrenal cortex from autoimmune inuences, tuberculosis and amyloidosis of metastatic neoplastic disease, results in
weakness, hypotension and generalized hyperpigmentation (Fig. 19.14). The
increased pigmentation may be particularly evident on the buccal mucosa and in
the palmar creases.
Androgenization (virilization)
This disorder of women is due to androgen-secreting tumours of the ovaries or
the adrenal cortex, but is usually due to polycystic ovaries in which there is an
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the excess hair is recent in onset and progressively becoming more noticeable
the hirsutes is accompanied by other physical signs including acne and
seborrhoea
there is signicant menstrual disturbance.
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NICOTINIC ACID
This is a water-soluble B vitamin found in grains and vegetables. Deciency
causes the condition of pellagra, resulting in diarrhoea, dementia and a photosensitivity dermatitis. The photosensitivity dermatitis develops a characteristic post-inammatory hyperpigmentation and is often very marked around
the neck.
KWASHIORKOR
This is due to severe protein deciency in children and is seen in the poorer,
underprivileged parts of the world, including areas of Africa and India.
Generalized oedema develops and the degree of skin pigmentation decreases. In
addition, the hair becomes reddish during the time of the deciency the socalled ag sign.
SENILE OSTEOPOROSIS
In this disorder of faulty bone mineralization due to vitamin D deciency, bone
thinning and multiple fractures, the skin becomes thinner and is almost transparent, with the veins being abnormally prominent (Fig. 19.16). The thinning can
be demonstrated by ultrasound.
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DERMATITIS HERPETIFORMIS
This itchy, blistering disorder is strongly associated with an absorptive defect of
the small bowel. Small-bowel mucosal biopsy demonstrates partial villous atrophy
in some 7080 per cent of patients with dermatitis herpetiformis. There are also
some minor functional absorptive abnormalities in most patients. This gut disorder is, in fact, a form of gluten enteropathy (as is coeliac disease) and can be
improved by a gluten-free diet.
PEUTZJEGHERS SYNDROME
This is a rare, autosomal dominant disorder in which perioral and labial pigmented macules occur in association with jejunal polyps. Pigmented macules also
occur over the ngers.
GARDENERS SYNDROME
In this dominant disorder, epidermoid cysts and benign epidermal tumours occur
in association with colonic polyposis.
Hepatic disease
In severe chronic hepatocellular liver failure, hypoalbuminaemia occurs, which
results in the curious sign of whitening of the ngernails (Fig. 19.17). Severe liver
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Summary
failure may also cause multiple spider naevi to develop over the arms, upper trunk
and face. These vascular anomalies consist of a central feeding blood vessel (the
body) with numerous ne radiating legs. Their cause is uncertain, but they may
be related to the plasma levels of unconjugated oestrogens.
In biliary cirrhosis, severe pruritus develops, resulting in excoriations and prurigo
papules. Jaundice and a generalized dusky pigmentation are seen in addition.
End-stage renal failure (uraemia) often causes persistent severe itch. The itch is
accompanied by a dusky, grey-brown pigmentation.
Obstructive jaundice from any cause results in intolerable itching.
Thyrotoxicosis sometimes causes itching, but does not seem to be due to the
sweatiness or increased warmth of the skin experienced by such patients.
Itching is sometimes a complaint of patients with hyperparathyroidism.
The symptom of itch is occasionally a sign of Hodgkins disease or, less often,
of another type of lymphoma. Rarely, the itch is a presenting symptom of the
neoplasm.
Itch is a well-known disabling complaint of patients with polycythaemia rubra
vera. For some curious reason, the itch may be a particular problem when these
patients have a bath.
It has often been claimed that patients with diabetes have pruritus, but if this
is the case, it must be extremely rare. Diabetics are prone to candidiasis, which
causes perigenital itch, and it is possible that this is how the idea began.
Summary
Certain skin disorders are precipitated by an
underlying malignancy. These include acanthosis
nigricans, erythema gyratum repens, acquired
ichthyosis and necrolytic migratory erythema.
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C H A P T E R
20
Disorders of
pigmentation
Generalized hypopigmentation
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Localized hypopigmentation
297
Hyperpigmentation
299
Summary
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Disorders of pigmentation
Dendrites
Nucleus
Nucleolus
Developing melanosomes
stages IIV
Generalized hypopigmentation
OCULOCUTANEOUS ALBINISM
There are several varieties of genetically determined defects in melanin synthesis,
the most common of which is recessively inherited oculocutaneous albinism.
Affected individuals have a very pale or even pinkish complexion with axen,
white or slightly yellowish hair and very light-blue or even pink eyes. Albinos are
also subject to nystagmus, either horizontal or rotatory. In addition, they are photophobic and often have serious refractive errors. They are extremely sensitive to the
harmful effects of solar irradiation and in sunny climates often develop skin cancers.
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Localized hypopigmentation
Albinos have a normal number of melanocytes in the basal layer of the epidermis, but lack tyrosinase and are unable to synthesize melanin. If hair is plucked and
incubated in a medium containing L-DOPA, the hair bulb does not turn black, as
it does normally.
Management
Albino patients must learn to protect themselves against UVR with sunscreens
and avoidance of sun wherever possible. Regular checking to detect early changes
of skin cancer is also important.
Localized hypopigmentation
PIEBALDISM
In this condition, there is a white forelock and white patches on the skin surface.
In Waardenburgs syndrome, the condition is associated with sensory deafness.
VITILIGO
Denition
This is a common skin disorder in which there is focal failure of pigmentation due
to destruction of melanocytes that is thought to be mediated by immunological
mechanisms.
Clinical features
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Disorders of pigmentation
(a)
(b)
Figure 20.4 (a) A sharply dened patch of vitiligo on the neck. (b) Vitiligo in a
dark-skinned patient.
Vitiligo occurs in 12 per cent of the population and is more common when it
has occurred in other members of the family. It is also more common in diabetes,
thyroid disease and alopecia areata, and appears to be due to an autoimmune
attack on melanocytes.
Treatment
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Hyperpigmentation
Comment
Vitiligo
Pityriasis versicolor
Pityriasis alba
Leprosy
White macules of
tuberous sclerosis
Naevus anaemicus
Chemical toxicity
Hyperpigmentation
It has to be determined whether the pigmentation is due to melanin or some other
pigment (Table 20.2).
Generalized melanin hyperpigmentation is seen in Addisons disease due to
destruction of the adrenal cortex from tuberculosis, autoimmune inuences, metastases or amyloidosis. Pigmentation is marked in the exures and exposed areas, but
the mucosae and nails are also hyperpigmented. The diagnosis is supported by
hypotension, hyponatraemia and extreme weakness. The hyperpigmentation is due
to an excess of pituitary peptides resulting from the lack of adrenal steroids. After
bilateral adrenalectomy, pigmentation may be extreme (Nelsons syndrome).
Generalized hyperpigmentation may be part of acanthosis nigricans (see
page 283), which is much more marked in the exures and is accompanied by
exaggerated skin markings and skin tags.
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Disorders of pigmentation
A bronzed appearance is seen in primary haemochromatosis (bronzed diabetes), in which iron is deposited in the viscera, including the pancreas (giving
rise to diabetes) and the liver (causing cirrhosis). The increased pigmentation is
caused by both iron and excess melaninization in the skin. Increased pigment is
also evident in secondary haemosiderosis. Generalized hyperpigmentation is also
seen in cirrhosis, particularly biliary cirrhosis, chronic renal failure, glycogen storage disease and Gauchers disease. Biliary cirrhosis and renal failure are usually
accompanied by severe pruritus.
Drugs can cause generalized diffuse hyperpigmentation, patchy generalized
or localized hyperpigmentation. Classic examples are due to the rare heavy metal
intoxications. Arsenic ingestion causes a generalized raindrop pattern of hyperpigmentation, and topical silver preparations cause argyria, producing a dusky,
greyish discoloration of the skin and mucosae.
Modern drugs can also produce darkening. Minoxycycline (Minocin) can
cause darkening of the scars of acne; it can also produce dark patches on exposed
areas. The pigment is a complex of iron, the drug and melanin and the condition
is only partially reversible. Amiodarone, the antiarrhythmic drug, causes a characteristic greyish colour on exposed sites. The phenothiazines, in high doses over
long periods, produce a purplish discoloration in the exposed areas due to the
deposition of a drugmelanin complex in the skin. Chlorpromazine is particularly
prone to doing this.
Carotenaemia produces an orange-yellow, golden hue due to the deposition
of beta-carotene in the skin. It is seen in food faddists who eat large amounts of
carrots and other red vegetables. Beta-carotene is also given for the condition of
erythropoietic protoporphyria (see page 261).
Canthexanthin is another carotenoid that produces a similar skin colour and
was sold for this purpose to simulate a bronzed suntan. Pigment crystals were
found in the retina of patients taking the drug and it has been withdrawn for this
reason.
Transient skin discoloration is seen in methaemoglobinaemia and sulphaemoglobinaemia due to dapsone administration.
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Hyperpigmentation
LOCALIZED HYPERPIGMENTATION
Mongolian spots, the naevus of Ota and the naevus of Ito are large, at, greybrown patches and can be confused with bruising and other conditions (Fig. 20.5).
Caf au lait patches are part of neurobromatosis (Von Recklinghausens disease,
see page 199). Numerous at, light-brown macules, which vary from 0.5 cm2 to
4 cm2 are present all over the skin surface and characteristically in the axillae
alongside the neurobromata (Fig. 20.6).
Not dissimilar brown macules are found on the lips and around the mouth and
on the ngers in PeutzJeghers syndrome, accompanied by small-bowel polyps,
and in Albrights syndrome, in which there are associated bone abnormalities.
A very common type of localized hyperpigmentation is chloasma. This facial
pigmentation may be part of the increased pigmentation of pregnancy or may
occur independently. The cheeks, periocular regions, forehead and neck may be
affected in this so-called mask of pregnancy (Fig. 20.7).
Post-inammatory hyperpigmentation may be due to melanocytic hyperplasia
occurring as part of epidermal thickening in chronic eczema, particularly atopic
eczema. This is transient and of no real consequence.
It may also be due to the shedding of melanin from the damaged epidermis
into the dermis, where it is engulfed by macrophages. This tattooing may last
many months. It is seen in lichen planus (Fig. 20.8; see also page 144) and in xed
drug eruption (see page 95).
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Disorders of pigmentation
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C H A P T E R
21
Management of
skin disease
Psychological aspects of skin disorder
303
Skin disability
305
305
309
Systemic therapy
311
314
Summary
316
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DELUSIONS OF PARASITOSIS
This is a rare psychosis in which the individual believes that his or her skin is
infested with insects or worms. Often, sufferers will bring to the doctor rolled up
horn or other skin debris and point proudly to the infesting insect. They may
point to blemishes on the skin as evidence of their problem. These patients beliefs
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are quite unshakeable, and beyond psychiatrists help. The drug pimozide has been
said to be helpful for patients with delusional parasitosis.
BODY IMAGE
We all have a particular view of ourselves and a special conceit over our own
visual worth. Curiously, some individuals have a distorted body image amounting
to a delusional belief. Too much hair, too little hair, discolorations and minor
blemishes can all become a major focal point of complaint. Dysmorphophobia is
a term used to describe this, not uncommon, condition.
Skin disability
Skin disease can be as disabling as disease of other organ systems. Disability from
skin disease consists of physical, emotional and social components. The physical
disability derives from decreased mobility due to the abnormal stratum corneum
present in eczema, psoriasis or the ichthyotic disorders. The abnormal horn lacks
extensibility and cracks when stretched. The abnormally stiff dermis in scleroderma
or scarring also affects mobility. The emotional disability stems from the psychological problems discussed above and can lead to serious depression and its consequences. The social disability stems from the isolation imposed by both the patients
themselves and society at large. It results in domestic and occupational problems.
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there is an adverse effect from use of the preparation (e.g. contact allergy)
the condition has been wrongly diagnosed
the patient has not used the medication
the condition is resistant to the treatment prescribed.
EMOLLIENTS
Emollients (moisturizers) act by occluding the skin surface with a lipid lm,
which prevents evaporation of water from the surface, allowing it to accumulate
within the stratum corneum. Emollients may be single-phase oils or greasy ointments, oil-in-water or water-in-oil emulsions, either as creams or lotions.
Emollients have important effects. They:
make the stratum corneum swell and atten so that the skin looks and feels
smoother
increase the extensibility of skin so that it cracks less
decrease binding forces between the horn cells and decrease scaling
decrease itch
have some intrinsic anti-inammatory properties, decrease epidermal mitotic
activity and have anti-prostaglandin synthetase activity.
Signicance
Photosensitivity
Acneiform folliculitis
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Uses of emollients
Emollients may be all that is required for patients with mild ichthyotic
disorders.
They are also useful for patients with eczema, particularly atopic dermatitis.
Emollients help patients with psoriasis and other chronic scaling dermatoses.
TOPICAL CORTICOSTEROIDS
There are numerous preparations containing topical corticosteroids, with different potencies (Table 21.2). Their predominant use is for eczematous dermatoses,
but they are also useful in psoriasis. They have marked anti-inammatory and
antiproliferative effects. A major part of their action is in inducing lipocortin the
endogenous inhibitor of phospholipase A2 which is important in the generation
of eicosanoid compounds involved in the inammatory process.
Adverse side effects from topical corticosteroids (Table 21.3)
Activity
Examples
Mild (weak)
Hydrocortisone
Clobetasone butyrate
Moderately potent
Flurandrenolone
Desoxymethasone
Potent
Betamethasone-17-valerate
Fluocinolone acetonide
Very potent
Clobetasone-17-propionate
Halcinonide
Ulabetasol
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skin thinning and striae (Fig. 21.4), resulting from the wasting action of corticosteroids on the dermal connective tissue
masked infection, particularly ringworm, resulting in extensive and unusualappearing ringworm (tinea incognito).
Note. Dilution of proprietary preparations is not advised because the formulations are complex and the important excipients are also diluted and may be ineffective when the dilution is made. Dilution does not necessarily decrease the effect
proportionately.
Case 22
Jeremy, aged 9, had had eczema since he was a few weeks of age, but it had
markedly worsened in the past 4 months, as had his asthma. Apart from the
obvious severe eczema, he had marked xeroderma. He started to improve when
he was treated regularly with emollients two or three times per day. He was also
helped by the use of a weak corticosteroid (clobetasone butyrate) twice daily and
a strong corticosteroid applied to the sites where there was severe eczema
(mometasone furoate) once daily. Care was taken to ensure that he did not use
excessive amounts of corticosteroids, in order to avoid the problems of skin
thinning and pituitaryadrenal axis suppression.
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All that weeps and contains pus is not infected: many inamed skin disorders
are exudative but not infected.
Some imidazole and older halogenated phenolic compounds may irritate;
some antibiotics (e.g. neomycin) sensitize.
It is quite easy to induce bacterial resistance, and agents that may be used
systemically should not be used topically.
Amongst the safest and most useful compounds for bacterial and fungal infections are the imidazoles (e.g. econazole, miconazole, isoconazole), the triazoles
(naftine, terbinane) and povidone iodine. The antibiotic mupirocin is very
useful. Aciclovir, famiciclovir and idoxuridine are antiviral preparations used for
herpes simplex, the rst of these also being used for herpes zoster.
There is a growing demand for the removal of moles, seborrhoeic warts and
similar benign lesions.
The incidence of skin cancers of all types is increasing.
There is increasing demand and ability to treat the skin changes of
photodamage.
BIOPSY
The removal of a small fragment of skin tissue by trephine (punch biopsy) for
routine histological preparation for electron microscopy, immunouorescence or
microbial culture is usually adequate. Sharp, disposable trephines are available of
26 mm in diameter. Sutures are not necessary for biopsies of less than 4 mm
diameter taken this way, and only occasionally for 4 mm trephines. The following
are useful tips for taking biopsies.
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ABLATIVE PROCEDURES
These are mainly used to treat seborrhoeic and viral warts and solar keratoses, but
also for minor, benign, localized lesions.
LASER TREATMENT
Lasers are high-intensity, coherent light sources of particular wavelengths, and are
employed for their destructive capacity. The particular tissue effect is inuenced
by the energy, the wavelength and the pulse duration of the emission, as well as by
the colour, thickness and depth of the tissue. Lasers are particularly useful for the
destruction of vascular birthmarks, but other kinds of lesions can also be tackled.
CRYOTHERAPY
This is used to treat viral warts and solar keratoses. A device supplying a ne spray
of liquid nitrogen is often used. The frozen skin turns snow white and needs to
stay this colour for 1520 seconds before tissue destruction is complete.
Caution is required when treating lesions on the ngers, as the digital nerves
can be damaged. Patients must be warned to expect pain and blistering at the
frozen site and be told to keep the site covered.
SHAVE EXCISIONS
This procedure is only suitable for benign, raised, dome-shaped lesions, such
as stable melanocytic naevi, as some abnormal tissue is left behind. After local
anaesthesia, the lesion is shaved off ush with the skin surface with a sharp scalpel.
The raw base is then lightly cauterized with an electrocautery loop. The tissue
removed is sent for histological examination.
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Systemic therapy
incision is parallel to Langers lines on the limbs and trunk but in the crease lines on
the face, scarring should be minimal. Keloid scars sometimes develop in patients aged
1230 years with excisions over the shoulders, upper arms and front of the chest.
Systemic therapy
In many cases, topical treatments are also available and decisions as to whether to
use a topical or a systemic agent need to be made. Some of the considerations are
as follows.
Systemic agents usually carry a greater risk of adverse side effects than topical
agents.
Systemic agents tend to have more potent therapeutic effects than topical
agents.
Many patients prefer a topical agent because they fear the side effects of
systemic treatment.
Some patients dislike using topical treatment and would prefer to take the risk
of side effects.
Topical treatment is impracticable in patients with widespread skin disease and
in the elderly and inrm.
The options need to be discussed with the patient.
SYSTEMIC CORTICOSTEROIDS
If these are needed, both the risks and the benets of such treatment should be
understood by all. Their action is predominantly suppressive by virtue of their
anti-inammatory properties. Systemic (and very potent topical) corticosteroids
can precipitate pustular psoriasis.
RETINOIDS
Although the usage of isotretinoin and acitretin differs, the precautions and side
effects are quite similar. There is a serious danger of teratogenicity if the drug is
given to a woman in the reproductive age group, and contraception is important.
Acitretin is mostly excreted quite quickly, but in the presence of alcohol is back
metabolized to the, now withdrawn, etretinate, which is stored in the fat and
detectable in the blood for 23 years. Contraception is required for this period.
Particular care must be taken with isotretinoin, as this drug is given for severe
acne and many young women are exposed to it. The mode of action of the
retinoid drugs is uncertain, but there appear to be fundamental effects on cellular
differentiation.
Patients on retinoids require monitoring for hepatotoxicity and elevation of
serum lipids every 48 weeks, and for bone toxicity annually.
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312
Usual dose
Main indications
Comments
Corticosteroids
550 mg daily
(prednisolone
equivalent)
Hypertension, diabetes,
osteoporosis, psychosis,
infections, gastrointestinal,
bleeding skin thinning and striae,
adrenocortical suppression
0.51.0 mg/kg
body weight daily
0.51.0 mg/kg
body weight daily
Severe acne
As above
Retinoids
Acitretin
Isotretinoin
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Methotrexate
525 mg weekly
Azathioprine
50150 mg daily
Nausea, myelosuppression
Cyclosporin
25 mg/kg body
weight daily
Severe psoriasis
(erythrodermic or
recalcitrant plaque type),
severe atopic dermatitis
Dapsone
25150 mg daily
Leprosy, dermatitis
herpetiformis
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METHOTREXATE
This is an antimetabolite that effectively stops cell division by blocking DNA synthesis. It also has many other metabolic effects. It is used both for its antiproliferative
actions and for its immunosuppressive effects. Patients require regular monitoring
for myelotoxicity and hepatotoxicity every 48 weeks and may need liver biopsies
after a cumulative dose of more than 1.5 g because of the frequency of serious liver
toxicity, particularly in those who abuse alcohol.
AZATHIOPRINE
This is an antimetabolite that also blocks DNA synthesis, whose prime use in dermatology is for its immunosuppressive activity. As with methotrexate, patients on
azathioprine require regular monitoring for myelotoxicity. Before use, the patient
should be checked for an inherited enzyme defect (thiopurine methyl transferase)
to avoid serious toxicity.
CYCLOSPORIN
This drug blocks lymphokine synthesis by lymphocytes. It is a very potent
immunosuppressive agent. Patients on the drug should be monitored for renal
toxicity and hypertension every 48 weeks.
DAPSONE (DIAMINOSULPHONE)
The mode of action of this drug is unclear. Its antimicrobial effects may be unrelated to its anti-inammatory activity. It causes haemolysis and methaemoglobinaemia and is myelotoxic.
ANTIFUNGALS
Griseofulvin, terbinane and itraconazole are effective against dermatophyte
infections. Itraconazole, uconazole and ketoconazole are effective against
infections with yeast-like micro-organisms. The doses and side effects are given
in Table 21.5.
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Dose
Indication
Side effects
Griseofulvin
0.51.0 g daily
Headaches, photosensitivities
Ketoconazole
200 mg daily
Amphotericin
Systemic candidiasis
Fluconazole
50 mg daily
Candidiasis, especially in
immunosuppressed patients
Nausea, rash
Itraconazole
100200 mg daily
Nausea
Terbinane
250 mg daily
Nausea, rash
of ultraviolet radiation (UVR) are often used in treatment. Natural sunshine can
also be used if the local weather conditions permit. Special spas have been established at the Dead Sea in Israel, around the Black Sea and elsewhere.
Treatment with the sunburn part of the UV spectrum (UVB: 280320 nm) is
sometimes used to treat patients with psoriasis. Caution is necessary to prevent
burning in the short term and chronic photodamage and skin cancers in the long
term by giving the minimum dose of UVR necessary to clear the patients problems.
PUVA treatment
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Summary
The skin is important in communication and there
is fear and dislike of skin disorders, causing social
isolation and depression in patients.
Stress may precipitate but not cause skin disorders.
Patients may produce a variety of lesions (dermatitis
artefacta). Rarely, patients may harbour a delusion
that their skin is infested by insects.
Dysmorphophobia describes the problem of
peoples distorted self-image (e.g. their nose is
too big, they have too much hair).
Skin disease may be both physically and
emotionally disabling.
In general, ointments are used for chronic scaling
disorders, whereas creams and lotions are used
for acute and exudative disorders.
Emollients occlude the skin surface, prevent
evaporation and cause a build up of water in the
stratum corneum. They soothe, smooth and soften
the skin. They have some anti-inammatory actions
and enhance desquamation. They are helpful for
patients with eczema, psoriasis and ichthyosis.
Topical corticosteroids are absorbed and may cause
pituitaryadrenal axis suppression with adrenal
cortical atrophy if appreciable amounts are applied
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Bibliography
Books of interest
Adler, M.W. (ed.) 1990 ABC of Sexually Transmitted Disease. London: BMJ
Publishing Group.
Ashton, R.E. (ed.) 1992 Differential Diagnosis in Dermatology (second edition).
Oxford: Radcliffe Medical Press.
Darmon, M. and Blumenberg, M. (eds) 1993 Molecular Biology of the Skin: the
keratinocyte. London: Academic Press.
Freinkel, R. and Woodley, D. (eds) 2001 The Biology of Skin. Carnforth: Parthenon.
Harper, J. (ed.) 1990 Handbook of Paediatric Dermatology. London: Butterworths.
Hawk, J.L.M. (ed.) 1999 Photodermatology. London: Arnold.
Levene, G.M. and Goolamali, S.K. (eds) 1986 Diagnostic Picture Tests in Dermatology.
London: Wolfe.
Lowe, N. and Marks, R. 1998 Retinoids. A Clinicians Guide (second edition).
London: Martin Dunitz.
McKee, P.H. 1999 Essential Skin Pathology. St Louis, MI: C.V. Mosby.
Marks, R. (ed.) 1981 Coping with Psoriasis. London: Sheldon Press.
Marks, R. (ed.) 1992 Eczema. London: Martin Dunitz.
Marks, R. (ed.) 1999 Skin Disease in Old Age (second edition). London: Martin
Dunitz.
Marks, R. 2001 Sophisticated Emollients. Stuttgart: Thieme International.
Marks, R. and Leyden, J.J. (eds) 2002 Dermatologic Therapy in Current Practice.
London: Martin Dunitz.
Marks, R. and Ortanne, J.P. 1999 Photodamaged Skin: clinical signs, causes and
management. London: Martin Dunitz.
Marks, R., Dykes, P.J. and Motley, R. 1993. Clinical Signs and Procedures in
Dermatology. London: Martin Dunitz.
Marks, R., Leveque, J.L. and Voegeli, R. (eds) 2002 The Essential Stratum Corneum.
London: Martin Dunitz.
Reonigk, R.K. and Roegnik, H.H. (eds) 1993 Surgical Dermatology. London:
Martin Dunitz.
Sharvill, D.E. (ed.) 1988 Skin Signs of Systemic Disease. London: Pocket Picture
Guides.
317
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Bibliography
Reference books
Braun-Falco, O., Plewig, G. et al. 2000. Dermatology. Berlin: Springer-Verlag.
Champion, R.H., Burton, J.L., Burns, D.A. and Breathnach, S.M. (eds) 1998 Textbook
of Dermatology (sixth edition, in four volumes). Oxford: Blackwell Science.
Goldsmith, L.A. (ed.) 1991 Physiology, Biochemistry and Molecular Biology of the
Skin (second edition). Oxford: Oxford University Press.
McKee, P.H. 1989 Pathology of the Skin with Clinical Correlations. Philadelphia,
PA: J.B. Lippincott Co.
318
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Index
Note: page numbers in bold refer to gures, page numbers in italics refer to information contained in tables
ablative procedures 310
acantholysis 92
acanthoma, clear cell 188, 189
acanthosis nigricans 283, 283, 299
aciclovir 51, 53, 100, 309
acitretin 311, 312
for chronic discoid lupus erythematosus 80
for lichen planus 147
for non-bullous ichthyosiform erythroderma
250
for psoriasis 141
for solar keratoses 210
acne 14961
clinical course 1523
clinical features 14951, 150, 151, 152
in Cushings syndrome 289
denition 149
disabling effects of 22
epidemiology 1534
pathology/aetiopathogenesis 1567, 156, 158
prevalence 2, 149
sites affected 152, 153
and sun exposure 34
treatment 15761, 159
systemic 15961, 159
topical 1579, 159
types 1546
acne from drugs and chemical agents
1545, 154
acne fulminans 15051
chloracne 1556
cosmetic 27, 27, 155, 155
cystic/nodulistic 15051
excoriated 156
infantile 154, 154, 2312, 232
oil acne 155, 155
acneiform folliculitis 155, 155
acrodermatitis chronica atrophicans 49
acrodermatitis continua 135
actinomycosis 43
adapalene 159
Addisons disease 14, 289, 289, 299
adrenalin 68, 93
agammaglobulinaemia, infantile 101
ageing process 234
see also old age; photodamage
extrinsic ageing 234
intrinsic ageing 234
AIDS (acquired immune deciency syndrome)
97100
see also HIV
and acquired ichthyosis 284
bacterial infections in 64, 99
fungal infections in 43, 98
pruritus in 99
psoriasis in 100, 138
scabies in 100
seborrhoeic dermatitis in 98, 98, 100, 100, 116
aspirin 74, 94
asthma 10910
ataxia telangiectasia 101
atherosclerosis 178
autoimmune disorders (collagen vascular
disorders) 7780, 100
see also lichen planus; lupus erythematosus
azathioprine 313, 314
for bullous pemphigoid 88
for chronic actinic dermatitis 32
for dermatomyositis 84
for eczema 236
for pemphigus 92
for polymorphic light eruption 33
for systemic lupus erythematosus 79
for systemic sclerosis 82
azelaic acid 168
bacterial skin infections 4450
see also specic infections
acute 445
in AIDS patients 64, 99
anthrax 46
carbuncles/furuncles 45
leishmaniasis 4950, 50
leprosy 489, 299
lupus vulgaris 467
Lyme disease 49
sarcoidosis 478, 478
tuberculosis 467, 176, 181
ulceration 172, 176, 181
balanitis xerotica obliterans 83
bandages
compression 177
rm pressure 198
basal cell carcinoma (basal cell epithelioma)
21417
clinical features/types 21516, 215, 215
morphoeic 215, 216, 216
nodulocystic 215, 215, 215
pigmented 215, 215, 215
supercial 132, 215, 216, 216
ulcerative 176, 182, 215, 215, 215
denition 214
degree of inltration 17
in the elderly 236
epidemiology 217
pathology/aetiopathogenesis 216, 217
treatment 217
basal cell naevus syndrome (Gorlins syndrome)
21718
baths, antimicrobial 113
Beaus lines 278
Beckers naevus 186, 186
bedbug (Cimex lectularius) 67
bee stings 67
benzoyl peroxide 157, 232
betadine 44
319
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Index
320
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Index
efavirenz 100
elastic tissue, naevi of 2001
elevation 176
emollients (moisturizers) 3067
for allergic contact dermatitis 125
for atopic dermatitis 11213, 230
for autosomal dominant ichthyosis 247
for bullous ichthyosiform erythroderma 251
for eczema 236
for juvenile plantar dermatosis 233
for napkin rash 230
for non-bullous ichthyosiform erythroderma
250
for use in old age 235, 236
for use in pregnancy 240
for psoriasis 138
for rosacea 168
for venous eczema 126
for xeroderma 246
endarterectomy 178
endocarditis, subacute bacterial 86
endocrine diseases 2858
environmental hazards 2536
chronic photodamage (photoageing) 2934,
30
cold injury 34
heat injury 35
solar UVR injury 278
toxic substances 267
eosinophilic granuloma (EG) 266
epidermal differentiation see keratinization
epidermal dysplasia 209
epidermal naevus 185
naevus unius lateris 185, 185
epidermal photodysplasia 29
epidermis
ageing 234
chronic photodamage to 29
in necrolytc migratory erythema 282, 282
psoriatic 136, 137, 137
and solar keratoses 207, 209
structure/functions 1, 46, 5
junction with the dermis 4, 5
pigmentation 295
toxic substance damage to 26
tumours 1836
epidermodysplasia verruciformis 55, 55
epidermolysis bullosa 9091
dystrophic epidermolysis bullosa 91
epidermolysis bullosa simplex 9091
Epidermophyton 39
E. occosum 39, 40, 41
epitheloid angiomatosis 99
erosions 19
eruptive skin disorders 12
see also drug eruptions; specic disorders
erysipelas 445, 45
erythema (redness) 1213
annular 77
in bullous ichthyosiform erythroderma 251
buttery 78, 78
in dermatomyositis 83, 84
erythema ab igne 35, 35
erythema chronicum migrans 49, 77
erythema gyratum repens 77, 283, 284
erythema induratum 467
erythema multiforme 56, 756, 756, 93
bullae 18, 19
causes 76, 76
clinical features 75
treatment 76
erythema nodosum 48, 77, 77, 77
gurative 285
necrolytc migratory 2812, 282
321
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Index
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Index
in leprosy 48
localized 2979, 299
hypothermia, infantile 228
hypotrichosis, congenital 268
hypovitaminosis A 101
iatrogenic disorders 307, 308
ichthyosis 15, 244
acquired 99, 254, 284, 285
autosomal dominant 2467, 247
lamellar 252, 252
sex-linked 2479, 248
idoxuridine 51, 309
imidazole, topical 309
for candidiasis 43
for pityriasis versicolor 39
for ringworm infections 42
for seborrhoeic dermatitis 116, 230
imiquimod 210
immune system imbalances 111
immunocompromised patients
see also AIDS; HIV
congenital immunodeciency 101
and deep fungus infections 43
drug-induced immunodeciency 1001, 101
and herpes zoster 52, 53
and scabies 5960, 61
immunouorescence techniques 147
direct 88, 90
indirect 92
immunoglobulin A (IgA) 89
immunoglobulin E (IgE) 93, 111
immunoglobulin G (IgG) 88, 89, 92
immunologically mediated disorders 240
of the skin 7196
see also pemphigus
annular erythemas 77
autoimmune disorders 7780, 100
blistering disease 879, 88
dermatitis herpetiformis 18, 19, 8990,
8990, 292
dermatomyositis 13, 13, 834, 84, 164, 2845
drug eruptions 925, 301
epidermolysis bullosa 9091
erythema multiforme 18, 19, 56, 756,
756, 76, 93
erythema nodosum 48, 77, 77, 77
morphoea 823, 82
systemic sclerosis 8082, 81, 81
urticaria and angioedema 715
vasculitis group of diseases 847, 857
impetiginization 19, 20
impetigo contagiosa 44, 44
in vitro spectroscopic method 31
indomethacin 93
infantile agammaglobulinaemia 101
infantile skin problems 22733
atopic dermatitis 228, 23031
cradle cap 116, 231
functional differences 227
infantile acne 154, 154, 2312, 232
juvenile plantar dermatosis 233
lip-licking cheilitis 233, 233
management problems 2278
napkin rash 22830
toxic epidermal necrolysis 2323
infections of the skin 3757
see also specic infections
bacterial see bacterial skin infections
fungal 3743, 98, 181
as sign of diabetes 288
viral see viral skin infections
infestations 5865, 6970
aetiology/epidemiology 589
helminthic 6970
pediculosis 635, 63, 64, 65
scabies 20, 5863, 5961, 62, 100
inammatory skin conditions
inammatory dermatitis 26, 26
oedema 17
psoriasis 137, 138
inositol nicotinate 34
insect bites/stings 58, 6570
bedbugs (Cimex lectularius) 67
bees/wasps 67
diseases spread by 66
eas 65
methods of skin injury 66
mites 67, 67
mosquitoes 65, 66
onchocerciasis 6970, 69
ticks 67
and urticaria 678, 68, 745
interferons 214, 223
recombinant 55, 100
interleukin-2 223
ischaemic ulcers 173, 1778
isomorphic response (Koebner phenomenon)
21, 130
isoniazid 46
isotretinoin (13-cis-retinoic acid)
systemic 311, 312
for acne 16061
for non-bullous ichthyosiform
erythroderma 250
for rosacea 167
side effects 160, 161, 250, 311, 312
for solar keratoses 210
topical 159
itraconazole, systemic 314, 315
for AIDS infections 100
for pityriasis versicolor 39
for ringworm infections 43
Ivermectin 70
JarischHerxheimer reaction 104
jaundice 293
juvenile melanoma 194, 194
juvenile plantar dermatosis 233
juvenile xanthogranuloma (JX) 2667
Kaposis sarcoma (idiopathic haemorrhagic
sarcoma) 99, 100, 2234, 223
KatzenbachMerritt syndrome 195
keloid scars 198, 198, 311
keratinization (epidermal differentiation)
disorders of 23, 24356
see also scaling
autosomal dominant ichthyosis 2467, 247
bullous ichthyosiform erythroderma
2512, 251, 252
collodion baby 249, 251, 2524, 253
Dariers disease 2545, 254
disability in 2445
ear deformities 252, 253
HaileyHailey disease 255
horn pearl formation 212, 213
lamellar ichthyosis 252, 252
non-bullous ichthyosiform erythroderma
24950, 250
pachyonychia congenital 256
primary 15, 15
secondary 15
sex-linked ichthyosis 2479, 248
tylosis 2556, 255
xeroderma 108, 21819, 219, 2456, 245,
246, 284
process of 3, 5, 243
keratinocytes
functions/structure 45, 296
large (cellules monstreuses) 211
and pigmentary incontinence 13
keratitis 165
keratoacanthoma (molluscum sebaceum) 214,
214
keratoconjunctivitis sicca 165
keratoderma blenorrhagica 102
keratolytic agents, topical
for autosomal dominant ichthyosis 247
for Dariers disease 255
for non-bullous ichthyosiform erythroderma
250
keratosis pilaris 246, 246
ketoconazole 100
systemic 423, 314, 315
topical 39
kwashiorkor 291
lactic acid 55
lamellar bodies (membrane-coating granules)
5
lamivudine 100
Langerhans cells
and ageing 234
in allergic contact dermatitis 125
in reticulohistiocytic proliferative disorders
2667
structure/functions 4, 6
Langers lines 26
laser treatment 310
leg, elevation 176
leiomyoma 21, 198
leishmaniasis 4950, 50
cutaneous component to visceral forms 50
cutaneous forms 49, 50
mucocutaneous forms 4950
leishmanin 50
lentigo maligna (Hutchinsons freckle) 21920,
219, 236
leper complex 212, 303
leprosy (Hansens disease) 489, 299
dimorphic 48
lepromatous form 489
multibacillary 48, 49
paucibacillary 48, 49
treatment 49
tuberculoid form 48
lesions
in acne 14951, 150, 151
in angioma 1945
in basal cell carcinoma 216, 217
of collagen and elastic tissue naevi 201
cystic 203, 204
denition 12
of granuloma annulare 265, 265
in Kaposis sarcoma 223, 224
in lentigo maligna 219
in lichen planus 144, 144
in malignant melanoma 222
in mastocytosis 202
in psoriasis 128, 129, 129
in rosacea 1623
in scabies 59, 59, 60
size/shape/thickness of 1517
annular (ring-like) 1617, 16
edges of 16
gurate 17
polygonal 17, 17
in squamous cell carcinoma 21112, 212
types
macules 15, 16
nodules 16
323
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lesions cont.
types cont.
plaques 15
tumours 16
LettererSiwe disease (LSD) 266
leucocytoclastic angiitis 85, 85
lhomme rouge 225
lice see pediculosis
lichen amyloidosis 262
lichen aureus 87
lichen planus 1447
aetiopathogenesis 1467, 146
clinical features 1446, 144, 145
clinical variants 1456
annular lichen planus 146
bullous lichen planus 146
hypertrophic lichen planus 145, 145
lichen nitidus 146
lichen plano-pilaris 146
denition 144
erythema of 13
isomorphic response 21
lesions of 17, 17
and localized hyperpigmentation 301, 302
and the nails 276, 277
and the scalp 275
treatment 147
lichen sclerosus et atrophicus 83
lichen simplex chronicus (circumscribed
neurodermatitis) 11921, 120, 131, 132
lichenication 19, 20, 20, 21
in atopic dermatitis 107, 1078, 109, 228, 230
in infancy 228, 228, 230
in lichen simplex chronicus 120, 120
lichenoid bands 209
lichenoid purpuric eruption 87
lip-licking cheilitis 233, 233
lipid histiocytes 262, 267, 287
lipocortin 307
lipomas 200
lithium succinate 116
lupus erythematosus 7880
chronic discoid lupus erythematosus (CDLE)
7980, 80
and sun exposure 34
systemic lupus erythematosus (SLE) 789,
78, 79, 163
in pregnancy 240
lupus pernio 48
lupus vulgaris 467
Lyme disease 49
lymphangioma circumscription 195, 195
lymphoedema 164
lymphomas of the skin (cutaneous T-cell
lymphoma) 2245
mycosis fungoides 2245, 225
Szary syndrome 225
lymphoreticular diseases 101
macular amyloidosis 262, 263
macules 15, 16
in lentigo maligna 219
in neurobromatosis 256, 301, 301
in PeutzJeghers syndrome 292
Madura foot 43
malathion 63, 64
malignancy
skin markers of 2815, 282
acanthosis nigricans 283, 283
acquired ichthyosis 284, 285
bullous pemphigoid 284
dermatomyositis 2845
erythema gyratum repens 283, 284
gurative erythemas 285
324
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Index
polymyositis 83
pores 2, 3, 34
porphyrias 25961
enzyme defects of 259, 260, 261
erythropoietic porphyria 261
erythropoietic protoporphyria 261, 300
hepatic 25960
porphyria cutanea tarda (PCT) 25960, 260,
261
porphyria variegata 261
port-wine stains 194, 194
potassium permanganate solution 113, 177
povidone iodine 309
prednisone 92
pregnancy 23842
effects on intercurrent skin disease 240
effects of intercurrent skin disease on the
fetus 24041
physiological changes in the skin 23840
skin disorders in 241
pressure sores 179
procainamide 95
Propionibacterium acnes 157
protein C deciency 173
prurigo nodularis 120, 120, 304
prurigo papules 19, 20, 21
pruritus (itching) 2021
in AIDS patients 99
in atopic dermatitis 107
in old age 235
in pregnancy 240, 241, 241
as sign of diabetes 288
systemic causes of 293
pseudoacanthosis nigricans 283
pseudoepitheliomatous hyperplasia 120
pseudomycelium 38
pseudopelade 275
psoralen drugs 141, 315
psoriasis 2, 12, 12842
aetiology 1378
in AIDS patients 100
clinical features 12830, 129, 130
clinical variants 1326
arthropathic psoriasis (arthritis mutilans)
1356, 136
erythrodermic psoriasis 4, 133, 139
exural 129, 130
guttate psoriasis 1323, 133
napkin psoriasis 133, 230, 231
pustular psoriasis 1345, 134, 135, 137, 139
denition 128
dehydration in 4
differential diagnosis 1312, 132
disabling effects of 22, 23
erythema of 13, 13
genetic inuences 131
in immunocompromised patients 100, 101
and the isomorphic response 21, 130
and keratinization 5
lesions of 1516
and the nails 276, 276
natural history/epidemiology 13031
painful 21
and the palms 132, 132
pathology/pathogenesis 1367
epidermal thickening 136, 136, 137, 138
inammatory component 137, 138
vascular component 137
scaling of 15
and sun exposure 34
treatment 13842, 31415
psychological aspects of skin disorder 213,
3035
psychotropic drugs 94
pus 45
pustular bacterid 135
pustules 150
pyoderma gangrenosum 18081, 180
pyogenic granuloma 197, 197
pyrazinamide 46
quinolones 160
radiotherapy
for basal cell carcinoma 217
for Kaposis sarcoma 224
for lentigo maligna 220
for squamous cell carcinoma 213
rashes
in allergic contact dermatitis 1223
in allergic vasculitis 84
blistering 94
in erythema multiforme 76
in exanthematic eruptions 94
infantile 22730
lichenoid 94, 119
lupus erythematosus-like 95
morbilliform 94
photosensitivity type 323, 33, 945, 94, 95
in pregnancy 241, 241
in primary irritant dermatitis 121
in rosacea 163
in scabies 589
sweat rashes 334
urticarial 94
in vascular eruptions 94
Raynauds phenomenon 34, 34, 80, 81, 82
recombinant interferons 55
recombinant interferon-alpha 2B 100
reectance spectroscopy 13
Refsums syndrome (heredopathia atactica
neuritisformis) 253
Reiters syndrome 102
renal allografts 101
renal failure 293, 300
reticulohistiocytic proliferative disorders 2667
retinoids 223
systemic 311, 312
for bullous ichthyosiform erythroderma
2512
for Dariers disease 255
for the harlequin fetus 253
for lichen planus 147
for non-bullous ichthyosiform
erythroderma 250
for pityriasis rubra pilaris 143
for psoriasis 140
for sex-linked ichthyosis 249
for solar keratoses 210
for squamous cell carcinoma 21314
teratogenicity of 140, 140, 160, 161, 240,
250, 311, 312
for xeroderma pigmentosum 218
topical
for acne 159
for chronic photodamage 29
for Kaposis sarcoma 224
for psoriasis 139
rhinophyma 164, 165, 166, 167
rifampicin 46, 49
ringworm see tinea infections
river blindness 69
rosacea 1628
aetiopathogenesis 1667, 167
clinical features 1623, 162, 163
complications 1645, 165
denition 162
differential diagnosis 1634, 164
326
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Index
treatment 104
and ulceration 103, 172, 181
syringoma 186, 187, 187
systemic diseases and the skin 28194
androgenization 28990, 290
diabetes 2868, 286
endocrine diseases 2858
gastrointestinal diseases 292
hepatic disease 2923, 293
nutrition 291
pruritus 293
skin markers of malignancy 2815, 282
systemic sclerosis 8082, 81
manifestations of 8081, 81
pathology 81
treatment 82
systemic therapy 31114, 31213
see also specic drugs
antifungals 314, 315
azathioprine 313, 314
comparison with topical treatments 310
corticosteroids 311
cyclosporin 313, 314
Dapsone 313, 314
methotrexate 313, 314
retinoids 311
T-cells 97, 111, 125
tacalcitol 138
tachyphylaxis 112
tacrolimus 112
tagretin 100
tar preparations
for atopic dermatitis 113
for juvenile plantar dermatosis 233
for lichen simplex chronicus 121
for psoriasis 138
tartrazine 94
tattooing, hyperpigmentary 27, 301
tazarotene 139, 141
telangiectasia 29, 30, 174, 174
ataxia telangiectasia 101
in rosacea 1623, 162, 166, 168
telangiectasia macularis eruptiva perstans of
Parkes Weber 202
telangiectatic macules 81, 81
telogen efuvium 273
teratogenicity, of systemic retinoids 140, 140,
160, 161, 240, 250, 311, 312
terbinane 42, 314, 315
testosterone 270
tetracyclines
eruptions due to 94, 95
systemic
for acne 15960
for perioral dermatitis 169
for rosacea 167
for seborrhoeic dermatitis 117
topical 159
theques 190, 191
thermal homeostasis 25
thiazide diuretics 94
thimble pitting 129, 276, 276
thinning of the skin 288, 288, 308
thioavine T 262
thiopurine methyl transferase deciency 314
thyroid acropachy 285
thyroid disease 2856, 293
tick bites 67
tinea (ringworm) infections 3943
differential diagnosis of 11516, 131, 131
lesions of 1617, 16
tinea capitis 39, 41, 41, 42
tinea corporis 3940, 39
327
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Index
328
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nodular vasculitis 86
polyarteritis nodosa 86
Vaseline 264
venereal disease, dermatological aspects 1024
chancroid 103
gonorrhoea 102
Reiters syndrome 102
syphilis 99, 1034, 103, 172, 181
Venereal Disease Reference Library (VDRL) test
104
venesection 260
venous drainage 1767
venous hypertension 1737, 174, 175, 178
venous ulceration 1256, 1737, 173, 175, 178
vesicants 27
vesicles
in eczema 18, 18
in herpes zoster 19
viral skin infections 5056
see also specic infections
in AIDS patients 989, 98
chicken pox 51, 52, 241
herpes simplex 5051, 51, 99, 100, 111, 241
herpes zoster 19, 21, 51, 523, 52, 99, 100
molluscum contagiosum 556, 55, 56, 98, 98
orf 56, 56
viral warts 535, 53, 54
vitamin A (retinol) 291
vitamin C (ascorbic acid) 291
vitamin D 291
vitamin D analogues 138, 139
vitiligo 2978, 298
Von Recklinghausens disease
(neurobromatosis) 16, 199200, 199, 256,
257, 301, 301
Von Zumbusch disease (generalized pustular
psoriasis) 1345, 135, 139
Waardenburgs syndrome 297
warts 241
differential diagnosis 185, 208
and drug-induced immunodeciency 101, 101
seborrhoeic 1845, 1845, 185, 205, 236
viral 535, 53, 54
wasp stings 67
Wassermann reaction (WR) 104
white dermatographism 109, 109
Wickhams striae 144, 144
winter itch 245
Woods light 38, 41
wound healing
delayed 1723
in the elderly 234
event sequence following 171, 172
important factors 1713
of ulceration 17182
xanthogranuloma, juvenile 2667
xanthomata 2624, 2878, 287
eruptive 264, 265
xanthelasma 264, 264
xanthoma disseminatum (XD) 2667
xanthoma tuberosum 264, 264
xeroderma 108, 2456, 284
causes 245, 245
keratosis pilaris 246, 246
treatment 246
xeroderma pigmentosum 21819, 219
zidovudine 100
ZiehlNielsen stain 48